park

Summary

Gene Symbol: park
Description: parkin
Alias: AAN12155.1, CG10523, Dmel\CG10523, Dpark, PARKIN, Park, Parkin, SD01679, dParkin, dpk, CG10523 gene product from transcript CG10523-RB, CG10523-PB, CG10523-PC, D-parkin, dparkin, park-PB, park-PC
Species: fruit fly

Top Publications

  1. pmc Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling
    Yufeng Yang
    Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA
    Proc Natl Acad Sci U S A 102:13670-5. 2005
  2. doi Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency
    Melissa Vos
    VIB Center for the Biology of Disease, Leuven, Belgium
    Science 336:1306-10. 2012
  3. pmc Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance
    Zhihao Wu
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Genes Dev 27:157-62. 2013
  4. pmc Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery
    Yufeng Yang
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 105:7070-5. 2008
  5. pmc The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila
    Hansong Deng
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 105:14503-8. 2008
  6. doi PINK1 controls mitochondrial localization of Parkin through direct phosphorylation
    YongSung Kim
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    Biochem Biophys Res Commun 377:975-80. 2008
  7. pmc Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin
    Alexander J Whitworth
    MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Sciences, University of Sheffield, Sheffield, S10 2TN, UK
    Dis Model Mech 1:168-74; discussion 173. 2008
  8. doi The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process
    Jeehye Park
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    Biochem Biophys Res Commun 378:518-23. 2009
  9. pmc Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo
    Jina Yun
    Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 28:14500-10. 2008
  10. pmc Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin
    L S Tain
    MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK
    Cell Death Differ 16:1118-25. 2009

Research Grants

Scientific Experts

  • Alexander J Whitworth
  • JOHN GERARD TOWER
  • Niki Chondrogianni
  • Andrew Rallis
  • Kiyoung Kim
  • Jae H Hur
  • Matthew Freeman
  • Jean Antoine Lepesant
  • Yuzuru Imai
  • Annika F M Haywood
  • Ethan Bier
  • Birgit Eisenhaber
  • M E Fortini
  • Jeehye Park
  • Jongkyeong Chung
  • Bingwei Lu
  • Yufeng Yang
  • Nidhi Saini
  • Giovanni Esposito
  • Ruth E Thomas
  • Song Liu
  • Patrik Verstreken
  • Angela C Poole
  • Melissa Vos
  • Sven Vilain
  • Saera Song
  • Leo J Pallanck
  • Verónica Muñoz-Soriano
  • Leo Pallanck
  • Ryosuke Takahashi
  • Li Zhang
  • Kyoung Sang Cho
  • Nobutaka Hattori
  • Jonathon L Burman
  • Stefanie Van Meensel
  • Onno Schaap
  • Konstanze F Winklhofer
  • Christopher J H Elliott
  • Evelyn S Vincow
  • Min Jung Lee
  • Soojin Hwang
  • Walter Schaffner
  • Young Joo Bae
  • Elena Ziviani
  • Sung Bae Lee
  • Laurie A Andrews
  • Mark W Dodson
  • YongSung Kim
  • Ming Guo
  • Stephan Gehrke
  • Ira E Clark
  • Saurabh Srivastav
  • Feng Gao
  • Sunhong Kim
  • Lichuan Yang
  • Jin Man Kim
  • M Flint Beal
  • Roberta Tufi
  • Juan A Navarro
  • Pontus Klein
  • Kahori Shiba-Fukushima
  • Aaron Voigt
  • Zhihao Wu
  • Benoit I Giasson
  • Yun Chen
  • Paolo S Manzanillo
  • Anil Rana
  • Tomoyo Sawada
  • Tomoko Kanao
  • I Pimenta de Castro
  • Dickon M Humphrey
  • Hyongjong Koh
  • Bart De Strooper
  • Chee Hoe Ng
  • Amanda Vincent
  • Yeun Su Choo
  • Vanessa A Morais
  • Selina Yu
  • Nicole Exner
  • Caroline Fernandes
  • Xinnan Wang
  • Cristina Ottone
  • Christian Haass
  • Zhuohua Zhang
  • Yoon Ki Hong
  • L M Martins
  • N Moisoi
  • Darae Kim
  • Oleg Georgiev
  • Meridith T Lorbeck

Detail Information

Publications86

  1. pmc Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling
    Yufeng Yang
    Department of Pathology, Stanford University School of Medicine, and Geriatric Research, Education and Clinical Center Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA
    Proc Natl Acad Sci U S A 102:13670-5. 2005
    ..We also observed impairment of PI3K/Akt signaling in the fly parkin model of PD, hinting at a common molecular event in the pathogenesis of PD...
  2. doi Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency
    Melissa Vos
    VIB Center for the Biology of Disease, Leuven, Belgium
    Science 336:1306-10. 2012
    ..Thus, mitochondrial dysfunction was rescued by vitamin K(2) that serves as a mitochondrial electron carrier, helping to maintain normal ATP production...
  3. pmc Tricornered/NDR kinase signaling mediates PINK1-directed mitochondrial quality control and tissue maintenance
    Zhihao Wu
    Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA
    Genes Dev 27:157-62. 2013
    ..Parkinson's disease-associated PINK1 and Parkin actively participate in MQC. However, the signaling events involved are largely unknown...
  4. pmc Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery
    Yufeng Yang
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Proc Natl Acad Sci U S A 105:7070-5. 2008
    ..These results reveal a cell biological role for Pink1 and establish mitochondrial fission/fusion as a paradigm for PD research. Compounds that modulate mitochondrial fission/fusion could have therapeutic value in PD intervention...
  5. pmc The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila
    Hansong Deng
    Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 105:14503-8. 2008
    Mutations in PTEN-induced kinase 1 (pink1) or parkin cause autosomal-recessive and some sporadic forms of Parkinson's disease. pink1 acts upstream of parkin in a common genetic pathway to regulate mitochondrial integrity in Drosophila...
  6. doi PINK1 controls mitochondrial localization of Parkin through direct phosphorylation
    YongSung Kim
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    Biochem Biophys Res Commun 377:975-80. 2008
    PTEN-induced putative kinase 1 (PINK1) and Parkin, encoded by their respective genes associated with Parkinson's disease (PD), are linked in a common pathway involved in the protection of mitochondrial integrity and function...
  7. pmc Rhomboid-7 and HtrA2/Omi act in a common pathway with the Parkinson's disease factors Pink1 and Parkin
    Alexander J Whitworth
    MRC Centre for Developmental and Biomedical Genetics, Department of Biomedical Sciences, University of Sheffield, Sheffield, S10 2TN, UK
    Dis Model Mech 1:168-74; discussion 173. 2008
    ..pathological cause, particularly with the identification of mutations in the PTEN-induced putative kinase (pink1), parkin and htrA2 (also known as omi) genes that are linked to PD...
  8. doi The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process
    Jeehye Park
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Republic of Korea
    Biochem Biophys Res Commun 378:518-23. 2009
    The two Parkinson's disease (PD) genes, PTEN-induced kinase 1 (PINK1) and parkin, are linked in a common pathway which affects mitochondrial integrity and function. However, it is still not known what this pathway does in the mitochondria...
  9. pmc Loss-of-function analysis suggests that Omi/HtrA2 is not an essential component of the PINK1/PARKIN pathway in vivo
    Jina Yun
    Department of Neurology, The David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA
    J Neurosci 28:14500-10. 2008
    ..as well as other, have previously shown that the Drosophila homologs of the familial PD genes, PINK1 (PARK6) and PARKIN (PARK2), function in a common genetic pathway to regulate mitochondrial integrity and dynamics...
  10. pmc Drosophila HtrA2 is dispensable for apoptosis but acts downstream of PINK1 independently from Parkin
    L S Tain
    MRC Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK
    Cell Death Differ 16:1118-25. 2009
    ..in Drosophila have provided valuable insight into the function of other PD-linked genes, in particular PINK1 and parkin, and their role in maintaining mitochondrial integrity...
  11. pmc Characterization of PINK1 (PTEN-induced putative kinase 1) mutations associated with Parkinson disease in mammalian cells and Drosophila
    Saera Song
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305 701, Republic of Korea
    J Biol Chem 288:5660-72. 2013
    ..However, PINK1 mutations in the kinase domain failed to translocate Parkin to mitochondria and to induce mitochondrial aggregation...
  12. pmc Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation
    A Kathrin Lutz
    Neurobiochemistry, Deutsches Zentrum für Neurodegenerative Erkrankungen and Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    J Biol Chem 284:22938-51. 2009
    Loss-of-function mutations in the parkin gene (PARK2) and PINK1 gene (PARK6) are associated with autosomal recessive parkinsonism...
  13. pmc Analysis of neural subtypes reveals selective mitochondrial dysfunction in dopaminergic neurons from parkin mutants
    Jonathon L Burman
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 109:10438-43. 2012
    Studies of the familial Parkinson disease-related proteins PINK1 and Parkin have demonstrated that these factors promote the fragmentation and turnover of mitochondria following treatment of cultured cells with mitochondrial depolarizing ..
  14. pmc Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss
    Luke S Tain
    Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield, UK
    Nat Neurosci 12:1129-35. 2009
    ..To discover potential therapeutic pathways, we identified factors that genetically interact with Drosophila park and Pink1...
  15. doi Leucine-Rich Repeat Kinase 2 interacts with Parkin, DJ-1 and PINK-1 in a Drosophila melanogaster model of Parkinson's disease
    Katerina Venderova
    Ottawa Health Research Institute, Neuroscience Research Institute, Ontario, Canada
    Hum Mol Genet 18:4390-404. 2009
    ..transgenic flies, various indices of the eye and dopaminergic survival were modified in a complex fashion by a concomitant expression of PINK1, DJ-1 or Parkin. This evidence suggests a genetic interaction between these PD-relevant genes.
  16. pmc The PINK1/Parkin pathway regulates mitochondrial morphology
    Angela C Poole
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 105:1638-43. 2008
    Loss-of-function mutations in the PTEN-induced kinase 1 (PINK1) or parkin genes, which encode a mitochondrially localized serine/threonine kinase and a ubiquitin-protein ligase, respectively, result in recessive familial forms of ..
  17. pmc Parkinson's disease-associated kinase PINK1 regulates Miro protein level and axonal transport of mitochondria
    Song Liu
    Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
    PLoS Genet 8:e1002537. 2012
    ..dMiro protein level was increased in dPINK1 mutant but decreased in dPINK1 or dParkin overexpression conditions...
  18. pmc Drosophila parkin requires PINK1 for mitochondrial translocation and ubiquitinates mitofusin
    Elena Ziviani
    Department of Biomedical Sciences, Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN, United Kingdom
    Proc Natl Acad Sci U S A 107:5018-23. 2010
    Loss of the E3 ubiquitin ligase Parkin causes early onset Parkinson's disease, a neurodegenerative disorder of unknown etiology...
  19. pmc The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway
    Angela C Poole
    Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
    PLoS ONE 5:e10054. 2010
    Loss-of-function mutations in the PINK1 or parkin genes result in recessive heritable forms of parkinsonism...
  20. pmc DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function
    Ling Yang Hao
    Department of Biology, Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 107:9747-52. 2010
    Mutations or deletions in PARKIN/PARK2, PINK1/PARK6, and DJ-1/PARK7 lead to autosomal recessive parkinsonism. In Drosophila, deletions in parkin and pink1 result in swollen and dysfunctional mitochondria in energy-demanding tissues...
  21. doi Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways
    Nidhi Saini
    Institute for Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH 8051 Zürich, Switzerland
    Neurobiol Dis 40:82-92. 2010
    ..Mutations in the parkin gene lead to autosomal recessive juvenile Parkinsonism (AR-JP)...
  22. pmc Silent information regulator 2 (Sir2) and Forkhead box O (FOXO) complement mitochondrial dysfunction and dopaminergic neuron loss in Drosophila PTEN-induced kinase 1 (PINK1) null mutant
    Hyongjong Koh
    Department of Pharmacology, Mitochondria Hub Regulation Center MHRC, Dong A University College of Medicine, Busan 602 714, Korea
    J Biol Chem 287:12750-8. 2012
    ..Moreover, another Parkinson disease-linked gene, parkin, functions downstream of PINK1 in protecting mitochondria and dopaminergic (DA) neuron...
  23. pmc Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster
    I Pimenta de Castro
    Cell Death Regulation, MRC Toxicology Unit, Leicester, UK
    Cell Death Differ 19:1308-16. 2012
    ..results in the activation of AMP-activated protein kinase-dependent autophagy and phenocopies of pink1 and parkin mutants...
  24. pmc Reduction of protein translation and activation of autophagy protect against PINK1 pathogenesis in Drosophila melanogaster
    Song Liu
    Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America
    PLoS Genet 6:e1001237. 2010
    Mutations in PINK1 and Parkin cause familial, early onset Parkinson's disease...
  25. pmc The loss of PGAM5 suppresses the mitochondrial degeneration caused by inactivation of PINK1 in Drosophila
    Yuzuru Imai
    Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
    PLoS Genet 6:e1001229. 2010
    ..Conversely, ectopic expression of dPGAM5 exacerbated the dPINK1 and Drosophila parkin (dParkin) phenotypes...
  26. pmc The yeast complex I equivalent NADH dehydrogenase rescues pink1 mutants
    Sven Vilain
    VIB Center for Biology of Disease, Katholieke Universiteit Leuven, Leuven, Belgium
    PLoS Genet 8:e1002456. 2012
    ..in Parkinson's disease, and loss of Pink1 function affects mitochondrial morphology via a pathway involving Parkin and components of the mitochondrial remodeling machinery...
  27. pmc PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility
    Xinnan Wang
    F M Kirby Neurobiology Center, Children s Hospital Boston, Boston, MA 02115, USA
    Cell 147:893-906. 2011
    ..We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement...
  28. pmc Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila
    Caroline Fernandes
    Department of Biology, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada
    Mol Brain 4:17. 2011
    Mutations in parkin and PTEN-induced kinase 1 (Pink1) lead to autosomal recessive forms of Parkinson's disease (PD). parkin and Pink1 encode a ubiquitin-protein ligase and a mitochondrially localized serine/threonine kinase, respectively...
  29. pmc Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila
    Guang Ho Cha
    National Creative Research Initiatives Center for Cell Growth Regulation, and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Kusong Dong, Yusong gu, Taejon 305 701, Korea
    Proc Natl Acad Sci U S A 102:10345-50. 2005
    b>Parkin, an E3 ubiquitin ligase, has been found to be responsible for autosomal recessive juvenile parkinsonism characterized primarily by selective loss of dopaminergic neurons with subsequent defects in movements...
  30. ncbi Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila
    Yufeng Yang
    Laboratory of Developmental Neurobiology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Neuron 37:911-24. 2003
    b>Parkin, an E3 ubiquitin ligase that degrades proteins with aberrant conformations, is associated with autosomal recessive juvenile Parkinsonism (AR-JP). The molecular basis of selective neuronal death in AR-JP is unknown...
  31. pmc Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants
    Jessica C Greene
    Department of Genome Sciences, University of Washington, P O Box 357730, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:4078-83. 2003
    ..Recently, loss-of-function mutations in the parkin gene, which encodes a ubiquitin-protein ligase, were found to underlie a familial form of PD known as autosomal ..
  32. pmc Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants
    Pontus Klein
    Molecules Signaling Development, Max Planck Institute of Neurobiology, Martinsried, Germany
    EMBO J 33:341-55. 2014
    Parkinson's disease (PD)-associated Pink1 and Parkin proteins are believed to function in a common pathway controlling mitochondrial clearance and trafficking...
  33. pmc PINK1-mediated phosphorylation of Parkin boosts Parkin activity in Drosophila
    Kahori Shiba-Fukushima
    Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan
    PLoS Genet 10:e1004391. 2014
    Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control...
  34. pmc Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson's disease
    Roberta Tufi
    MRC Toxicology Unit, Lancaster Road, Leicester LE1 9HN, UK
    Nat Cell Biol 16:157-66. 2014
    ..We propose that targeting strategies enhancing nucleotide synthesis pathways may reverse mitochondrial dysfunction and rescue neurodegeneration in PD and, potentially, other diseases linked to mitochondrial impairment. ..
  35. ncbi Drosophila parkin mutants have decreased mass and cell size and increased sensitivity to oxygen radical stress
    Yakov Pesah
    Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA
    Development 131:2183-94. 2004
    Mutations in the gene parkin in humans (PARK2) are responsible for a large number of familial cases of autosomal-recessive Parkinson disease...
  36. ncbi RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity
    Ling Zhong
    Department of Medicine, Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 280:9425-30. 2005
    b>Parkin is a ubiquitin-protein isopeptide ligase. It has been suggested that loss of function in parkin causes accumulation and aggregation of its substrates, leading to death of dopaminergic neurons in Parkinson disease...
  37. pmc Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease
    Alexander J Whitworth
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 102:8024-9. 2005
    Loss-of-function mutations of the parkin gene are a major cause of early-onset parkinsonism. To explore the mechanism by which loss of parkin function results in neurodegeneration, we are using a genetic approach in Drosophila...
  38. ncbi Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin
    Jeehye Park
    Nature 441:1157-61. 2006
    ..Notably, we also found that PINK1 mutants share marked phenotypic similarities with parkin mutants...
  39. ncbi Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin
    Ira E Clark
    Nature 441:1162-6. 2006
    ..familial forms of Parkinson's disease have been identified, including PTEN-induced kinase 1 (PINK1; PARK6) and parkin (PARK2), which are also associated with sporadic forms of Parkinson's disease...
  40. pmc Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan
    Anil Rana
    Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA
    Proc Natl Acad Sci U S A 110:8638-43. 2013
    ..Loss-of-function mutations in parkin, an E3 ubiquitin ligase that functions to promote the ubiquitin-proteasome system of protein degradation and also ..
  41. pmc Aconitase causes iron toxicity in Drosophila pink1 mutants
    Giovanni Esposito
    VIB Center for the Biology of Disease, Leuven, Belgium
    PLoS Genet 9:e1003478. 2013
    ..leads to defects in mitochondrial function, and genetic data suggest that another PD-related gene product, Parkin, acts with pink1 to regulate the clearance of dysfunctional mitochondria (mitophagy)...
  42. pmc Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin
    Yufeng Yang
    Department of Pathology and Geriatric Research, Education and Clinical Center Veterans Affairs Palo Alto Health Care System, Stanford University School of Medicine, Palo Alto, CA 94304, USA
    Proc Natl Acad Sci U S A 103:10793-8. 2006
    ..The muscle and dopaminergic phenotypes associated with dPink1 inactivation show similarity to that seen in parkin mutant flies and could be suppressed by the overexpression of Parkin but not DJ-1...
  43. pmc PINK1-phosphorylated mitofusin 2 is a Parkin receptor for culling damaged mitochondria
    Yun Chen
    Center for Pharmacogenomics, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    Science 340:471-5. 2013
    ..putative kinase protein 1; PTEN is phosphatase and tensin homolog) and the cytosolic ubiquitin ligase Parkin. The nature of the PINK-Parkin interaction and the identity of key factors directing Parkin to damaged ..
  44. pmc TRAP1 rescues PINK1 loss-of-function phenotypes
    Li Zhang
    Department of Neurology, University Medical Center, RWTH Aachen, Aachen D 52074, Germany
    Hum Mol Genet 22:2829-41. 2013
    ..Here we investigated the potential of TRAP1 to rescue dysfunction induced by either PINK1 or Parkin deficiency in vivo and in vitro...
  45. ncbi The Drosophila parkin homologue is required for normal mitochondrial dynamics during spermiogenesis
    Maria Giovanna Riparbelli
    University of Siena, Department of Evolutionary Biology, Via A Moro 4, I 53100 Siena, Italy
    Dev Biol 303:108-20. 2007
    Drosophila parkin, the ortholog of the human parkin gene, responsible for a familiar form of autosomal recessive juvenile parkinsonism, has been shown previously to be involved in Drosophila male fertility...
  46. pmc The PINK1-Parkin pathway promotes both mitophagy and selective respiratory chain turnover in vivo
    Evelyn S Vincow
    Neurobiology and Behavior Program and Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 110:6400-5. 2013
    ..Recently, in vitro studies of the PD-related proteins Parkin and PINK1 have found that these factors act in a common pathway to promote the selective autophagic degradation of ..
  47. ncbi Drosophila overexpressing parkin R275W mutant exhibits dopaminergic neuron degeneration and mitochondrial abnormalities
    Cheng Wang
    Neurodegeneration Research Laboratory, National Neuroscience Institute, Singapore 308433
    J Neurosci 27:8563-70. 2007
    Mutations in the parkin gene are a predominant cause of familial parkinsonism...
  48. doi Zinc supplement greatly improves the condition of parkin mutant Drosophila
    Nidhi Saini
    Institute of Molecular Life Sciences, University of Zurich, Switzerland
    Biol Chem 391:513-8. 2010
    ..Mutations in the gene encoding Parkin, a ubiquitin ligase, are responsible for a familial form of PD...
  49. ncbi Genomic organization and expression of parkin in Drosophila melanogaster
    Young Joo Bae
    Department of Biological Science, College of Natural Science, Ewha Womans University, Seoul 120 750, Korea
    Exp Mol Med 35:393-402. 2003
    ..melanogaster homolog of human parkin. The 2,122 bp parkin gene sequence contains six exons that form a 1,449 bp transcript encoding a protein of 482 ..
  50. doi Analysis of dopaminergic neuronal dysfunction in genetic and toxin-induced models of Parkinson's disease in Drosophila
    Juan A Navarro
    Institute of Zoology, University of Regensburg, Regensburg, Germany
    J Neurochem 131:369-82. 2014
    ..an attempt to re-evaluate and clarify this issue, we have examined three different genetic (α-synuclein, Pink1, parkin) and two toxin-based (rotenone and paraquat) models of the disease for neuronal cell loss...
  51. doi The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway
    Feng Gao
    Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro Psycho Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China, Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science and Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China and
    Hum Mol Genet 24:2528-38. 2015
    ..BNIP3L rescues mitochondrial defects in pink1 mutant Drosophila but not in park mutant Drosophila, indicating that the clearance of mitochondria induced by BNIP3L depends on the presence of PARK2...
  52. pmc Complex-I-ty in aging
    Jae H Hur
    Department of Biology, Harvey Mudd College, Claremont, CA, 91711, USA
    J Bioenerg Biomembr 46:329-35. 2014
    ..We suggest that manipulations that increase or decrease complex I activity both converge on improved mitochondrial homeostasis during aging, resulting in prolonged lifespan. ..
  53. pmc PINK1-Parkin pathway activity is regulated by degradation of PINK1 in the mitochondrial matrix
    Ruth E Thomas
    Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 10:e1004279. 2014
    ..that the processed forms of PINK1 that accumulate upon Lon inactivation are capable of activating the PINK1-Parkin pathway in vivo...
  54. pmc Regulation of parkin and PINK1 by neddylation
    Yeun Su Choo
    Sanford Burnham Medical Research Institute, 10901 N Torrey Pines Road, La Jolla, CA 92037, USA
    Hum Mol Genet 21:2514-23. 2012
    ..Here, we report that Parkinson's disease (PD)-related parkin and PINK1 are NEDD8 conjugated...
  55. pmc The ubiquitin ligase parkin mediates resistance to intracellular pathogens
    Paolo S Manzanillo
    Department of Microbiology and Immunology Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California 94158, USA
    Nature 501:512-6. 2013
    ..The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) ..
  56. doi Glutathione S-transferase omega suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila
    Kiyoung Kim
    Department of Medical Biotechnology, Soonchunhyang University, Asan Si, Republic of Korea
    Biochem Biophys Res Commun 437:615-9. 2013
    ..is a phase II detoxification enzyme that conjugates targets to glutathione, and has recently been implicated in parkin-associated PD...
  57. doi Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons in Drosophila model of Parkinson's disease
    Saurabh Srivastav
    Cell and Neurobiology Laboratory, Department of Biochemistry, Faculty of Science, Banaras Hindu University, India
    Biochem Biophys Res Commun 460:780-5. 2015
    b>parkin loss associated early-onset of Parkinson's disease, involves mitochondrial dysfunction and oxidative stress as the plausible decisive molecular mechanisms in disease pathogenesis...
  58. pmc parkin-induced defects in neurophysiology and locomotion are generated by metabolic dysfunction and not oxidative stress
    Amanda Vincent
    Department of Biology, University of York, P O Box 373, York YO10 5YW, UK
    Hum Mol Genet 21:1760-9. 2012
    ..In this study, we demonstrate that the larva of the Drosophila parkin mutant faithfully models the locomotory and metabolic defects of PD and is an excellent system for investigating ..
  59. pmc The effects of hempseed meal intake and linoleic acid on Drosophila models of neurodegenerative diseases and hypercholesterolemia
    Min Jung Lee
    Department of Biological Sciences, Konkuk University, Seoul, 143 701, Korea
    Mol Cells 31:337-42. 2011
    ..In conclusion, our results indicate that HSM and linoleic acid exert inhibitory effects on both Aβ42 cytotoxicity and cholesterol uptake, and are potential candidates for the treatment of Alzheimer's disease and cardiovascular disease...
  60. pmc The histone demethylase Dmel\Kdm4A controls genes required for life span and male-specific sex determination in Drosophila
    Meridith T Lorbeck
    Department of Biology, Drexel University, Philadelphia, PA 19104, USA
    Gene 450:8-17. 2010
    ..Our results have implications for the role of the epigenetic regulator Dmel\Kdm4A in the control of genes involved in life span and male-specific sex determination in the fly...
  61. doi Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila
    Dickon M Humphrey
    MRC Centre for Neurodegeneration Research, King s College London, Institute of Psychiatry, Department of Neuroscience, King s College London, London, UK
    Hum Mol Genet 21:2698-712. 2012
    ..Using this model, we find that associated lethality can be partially rescued by targeting PINK1/parkin signaling or Drp1, both of which have been implicated in mitochondrial dynamics and Parkinson's disease...
  62. doi Septin 4, the drosophila ortholog of human CDCrel-1, accumulates in parkin mutant brains and is functionally related to the Nedd4 E3 ubiquitin ligase
    Verónica Muñoz-Soriano
    Departamento de Genetica, Facultad de CC Biológicas, Universidad de Valencia, Dr Moliner 50, Burjassot, 46100, Valencia, Spain
    J Mol Neurosci 48:136-43. 2012
    ..Although most PD cases are sporadic, several loci have been involved in the disease. parkin (PARK) is causative of autosomal recessive juvenile Parkinsonism (ARJP) and encodes an E3 ubiquitin ligase ..
  63. pmc Stable isotope labeling and label-free proteomics of Drosophila parkin null mutants
    Zhiyin Xun
    Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA
    J Proteome Res 8:4500-10. 2009
    ..Loss-of-function mutations in parkin which encodes an E3 ubiquitin protein ligase contribute to a predominant cause of a familial form of PD termed ..
  64. doi In vivo measurement of muscle output in intact Drosophila
    Christopher J H Elliott
    Department of Biology, University of York, York YO10 5DD, UK
    Methods 56:78-86. 2012
    ..We have now extended the use of the apparatus to record the muscle forces during larval and other aspects of adult locomotion. The robustness, simplicity and versatility of the apparatus are key to these measurements...
  65. doi AMP kinase activation mitigates dopaminergic dysfunction and mitochondrial abnormalities in Drosophila models of Parkinson's disease
    Chee Hoe Ng
    National Neuroscience Institute, Singapore 308433
    J Neurosci 32:14311-7. 2012
    Mutations in parkin and LRRK2 together account for the majority of familial Parkinson's disease (PD) cases. Interestingly, recent evidence implicates the involvement of parkin and LRRK2 in mitochondrial homeostasis...
  66. ncbi Drosophila melanogaster Parkin ubiquitinates peanut and septin1 as an E3 ubiquitin-protein ligase
    Young Joo Bae
    Laboratory of Genetics, Department of Life Science, College of Natural Science, Seoul 120 750, Republic of Korea
    Insect Biochem Mol Biol 37:430-9. 2007
    ..juvenile parkinsonism (AR-JP), a common familial form of Parkinson's disease, is caused by mutations of human Parkin. To deepen the understanding of Parkin biology in an in vivo model of Drosophila, we attempted to characterize the ..
  67. pmc Parkin counteracts symptoms in a Drosophila model of Parkinson's disease
    Annika F M Haywood
    Department of Biology, Memorial University of Newfoundland, St John s, Newfoundland and Labrador, A1B 3X9, Canada
    BMC Neurosci 5:14. 2004
    ..Two inherited forms of PD have been linked to mutations in the alpha-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation...
  68. pmc The ubiquitin proteasome system in synaptic and axonal degeneration: a new twist to an old cycle
    Laura Korhonen
    Dept of Neuroscience, Unit of Neurobiology, Biomedical Centre, Box 587, Uppsala University, S 75123 Uppsala, Sweden
    J Cell Biol 165:27-30. 2004
    ..Increased knowledge of the UPS in synaptic and axonal reactions may provide novel drug targets for treatments of neuronal injuries and neurodegenerative disorders...
  69. ncbi blistery encodes Drosophila tensin protein and interacts with integrin and the JNK signaling pathway during wing development
    Sung Bae Lee
    National Creative Research Initiatives Center for Cell Growth Regulation and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon 305 701, Korea
    Development 130:4001-10. 2003
    ....
  70. ncbi Are ubiquitination pathways central to Parkinson's disease?
    Benoit I Giasson
    Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cell 114:1-8. 2003
    ....
  71. ncbi The cellular protein level of parkin is regulated by its ubiquitin-like domain
    Natalie Finney
    Nervous System Research, Novartis Pharma AG, CH 4002 Basel, Switzerland
    J Biol Chem 278:16054-8. 2003
    b>Parkin is a ubiquitin-protein isopeptide ligase (E3) involved in ubiquitin/proteasome-mediated protein degradation. Mutations in the parkin gene cause a loss-of-function and/or alter protein levels of parkin...
  72. ncbi Immunodetection of Parkin protein in vertebrate and invertebrate brains: a comparative study using specific antibodies
    J M Horowitz
    Medaille College, Social Sciences, Buffalo, NY 14214, USA
    J Chem Neuroanat 21:75-93. 2001
    b>Parkin is an intracellular protein that plays a significant role in the etiopathogenesis of autosomal recessive juvenile parkinsonism...
  73. pmc A survey of human disease gene counterparts in the Drosophila genome
    M E Fortini
    Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Cell Biol 150:F23-30. 2000
  74. ncbi A view of mount Drosophila
    J Hodgkin
    Nature 404:442-3. 2000
  75. ncbi Fly meets shotgun: shotgun wins
    D L Hartl
    Nat Genet 24:327-8. 2000
  76. ncbi Mutant alpha-synuclein-induced degeneration is reduced by parkin in a fly model of Parkinson's disease
    Annika F M Haywood
    Department of Biology, Memorical University of Newfoundland, St John s, Canada
    Genome 49:505-10. 2006
    ..Mutations in the genes that encode alpha-synuclein and parkin have been linked to inherited forms of this disease...
  77. ncbi Neurodegenerative disease: pink, parkin and the brain
    Leo Pallanck
    Nature 441:1058. 2006
  78. ncbi Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning
    Chay T Kuo
    Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, California 94143, USA
    Neuron 51:283-90. 2006
    ..Thus, in addition to uncovering E2/E3 ubiquitinating enzymes for dendrite pruning, this study provides a mechanistic link between UPS and the apoptotic machinery in regulating neuronal process remodeling...
  79. pmc Antioxidants put Parkinson flies back in the PINK
    Ethan Bier
    Department of Biology, University of California at San Diego, La Jolla, CA 92093 0349, USA
    Proc Natl Acad Sci U S A 103:13269-70. 2006
  80. ncbi Overexpression of Septin 4, the Drosophila homologue of human CDCrel-1, is toxic for dopaminergic neurons
    Verónica Muñoz-Soriano
    Departamento de Genetica, Facultad CC Biológicas, University of Valencia, Doctor Moliner 50, E 46100 Burjasot, Spain
    Eur J Neurosci 26:3150-8. 2007
    b>parkin loss-of-function mutations are linked to autosomal recessive juvenile parkinsonism. Parkin is an E3 ubiquitin ligase that promotes degradation of specific target proteins by the proteasome...
  81. pmc Clueless, a conserved Drosophila gene required for mitochondrial subcellular localization, interacts genetically with parkin
    Rachel T Cox
    Department of Embryology Howard Hughes Medical Institute, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA
    Dis Model Mech 2:490-9. 2009
    Parkinson's disease has been linked to altered mitochondrial function. Mutations in parkin (park), the Drosophila ortholog of a human gene that is responsible for many familial cases of Parkinson's disease, shorten life span, abolish ..
  82. pmc Drosophila histone deacetylase 6 protects dopaminergic neurons against {alpha}-synuclein toxicity by promoting inclusion formation
    Guiping Du
    National Laboratory of Macromolecules and State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
    Mol Biol Cell 21:2128-37. 2010
    ..We propose that alpha-synuclein inclusion formation in the presence of dHDAC6 protects DA neurons from being damaged by oligomers, which may uncover a common mechanism for synucleinopathies...
  83. doi Parkin suppresses c-Jun N-terminal kinase-induced cell death via transcriptional regulation in Drosophila
    Soojin Hwang
    Department of Biological Sciences, Konkuk University, Seoul, 143 701, Korea
    Mol Cells 29:575-80. 2010
    b>Parkin is the most prevalent genetic factor in the onset of autosomal recessive juvenile parkinsonism (AR-JP), and mutations in parkin has been reported to cause motor defects, which result from dopamine deficiency caused by dopaminergic ..
  84. doi Diminution of eIF4E activity suppresses parkin mutant phenotypes
    Cristina Ottone
    CEINGE Biotecnologie Avanzate, Via Comunale Margherita 482, 80145 Naples, Italy
    Gene 470:12-9. 2011
    Mutations in the human parkin (PARK2) gene cause autosomal recessive-juvenile Parkinson's disease (AR-JP). In Drosophila melanogaster, mutant parkin alleles display a broad range of phenotypic alterations, including female infertility...
  85. pmc The parkin mutant phenotype in the fly is largely rescued by metal-responsive transcription factor (MTF-1)
    Nidhi Saini
    Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
    Mol Cell Biol 31:2151-61. 2011
    The gene for Parkin, an E3 ubiquitin ligase, is mutated in some familial forms of Parkinson's disease, a severe neurodegenerative disorder...

Research Grants6

  1. 2003 Gordon Research Conference - Biology of Aging
    John Tower; Fiscal Year: 2003
    ..Significant funding is also provided by the Gordon Research Conference Organization, and additional funds are being solicited from private foundations and industry. ..
  2. DROSOPHILA LONGEVITY ASSURANCE GENES
    John Tower; Fiscal Year: 2003
    ..PdL creates dominant conditional mutations, which should greatly facilitate the identification, characterization and cloning of novel Drosophila LAGs. ..
  3. Drosophila DNA Replication Origins
    John Tower; Fiscal Year: 2005
    ..The experiments will test a number of specific hypotheses as to the organization and regulation of the chorion locus DNA replication origins. ..
  4. Genetic Analysis of Bacterial Toxins in Drosophia
    Ethan Bier; Fiscal Year: 2005
    ..DN alleles 2-2: Characterize molecular lesion in DN-toxin NOVA alleles 2-3: Confirm that DN-toxin alleles interfere with wild-type toxin gene function 2-4: Determine whether DN-toxin alleles function in mammalian cells ..
  5. Analysis of Early Wing Vein Development in Drosophila
    Ethan Bier; Fiscal Year: 2007
    ..Thus, knowledge gained from these studies should have broad applications to understanding vertebrate development as well as offering possible insights into mechanisms of human disease. ..
  6. MOLECULAR GENETICS OF EARLY NEUROGENESIS
    Ethan Bier; Fiscal Year: 2010
    ..These studies may provide the framework for our future studies relevant to human disease and drug abuse. ..