Genomes and Genes
Gene Symbol: Drp1
Description: Dynamin related protein 1
Alias: CG3210, DRP, DRP1, Dmel\CG3210, Dnm1/Drp1, Drp, Drp-1, drp-1, drp1, frat, l(2)22Fc, l(2)22Fd, l(2)ND2, l(2)ND3, dynamin related protein 1, CG3210-PA, CG3210-PB, Drp1-PA, Drp1-PB, dynamin related protein-1, dynamin-2, dynamin-related protein, dynamin-related protein 1, dynaminrelated protein 1, fratboy, lethal(2)22Fc, lethal(2)22Fd, near dpp complementation group 2, near dpp complementation group 3, noodle
Species: fruit fly
- Goyal G, Fell B, Sarin A, Youle R, Sriram V. Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster. Dev Cell. 2007;12:807-16 pubmed..Using genetic mutants and RNAi-mediated knockdown of drp-1, we find that Drp-1 not only regulates mitochondrial fission in normal cells, but mediates mitochondrial ..
- Poole A, Thomas R, Andrews L, McBride H, Whitworth A, Pallanck L. The PINK1/Parkin pathway regulates mitochondrial morphology. Proc Natl Acad Sci U S A. 2008;105:1638-43 pubmed publisher..We report that heterozygous loss-of-function mutations of drp1, which encodes a key mitochondrial fission-promoting component, are largely lethal in a PINK1 or parkin mutant ..
- Aldridge A, Benson L, Siegenthaler M, Whigham B, Stowers R, Hales K. Roles for Drp1, a dynamin-related protein, and milton, a kinesin-associated protein, in mitochondrial segregation, unfurling and elongation during Drosophila spermatogenesis. Fly (Austin). 2007;1:38-46 pubmed..b>Drp1 encodes a dynamin-related protein whose homologs in many organisms mediate mitochondrial fission and whose ..
- Lutz A, Exner N, Fett M, Schlehe J, Kloos K, Lämmermann K, et al. Loss of parkin or PINK1 function increases Drp1-dependent mitochondrial fragmentation. J Biol Chem. 2009;284:22938-51 pubmed publisher..rescued by the mitochondrial fusion proteins Mfn2 and OPA1 or by a dominant negative mutant of the fission protein Drp1. Both parkin and PINK1 were able to suppress mitochondrial fragmentation induced by Drp1...
- Esposito G, Vos M, Vilain S, Swerts J, De Sousa Valadas J, Van Meensel S, et al. Aconitase causes iron toxicity in Drosophila pink1 mutants. PLoS Genet. 2013;9:e1003478 pubmed publisher..Thus our data indicate that superoxide-dependent [4Fe-4S] inactivation defines a potential pathogenic cascade that acts independent of mitophagy and links iron toxicity to mitochondrial failure in a PD-relevant model. ..
- Park J, Kim Y, Choi S, Koh H, Lee S, Kim J, et al. Drosophila Porin/VDAC affects mitochondrial morphology. PLoS ONE. 2010;5:e13151 pubmed publisher..Furthermore, increased mitochondrial fission by Drp1 expression suppressed the flight defects in the porin mutants...
- Venken K, He Y, Hoskins R, Bellen H. P[acman]: a BAC transgenic platform for targeted insertion of large DNA fragments in D. melanogaster. Science. 2006;314:1747-51 pubmed..This transgenesis platform should greatly facilitate structure/function analyses of most Drosophila genes...
- Deng H, Dodson M, Huang H, Guo M. The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105:14503-8 pubmed publisher..fusion, controlled by Mitofusin (mfn) and Optic atrophy 1 (opa1), and mitochondrial fission, controlled by drp1. Here, we explore interactions between pink1/parkin and the mitochondrial fusion/fission machinery...
- Liu W, Acin Perez R, Geghman K, Manfredi G, Lu B, Li C. Pink1 regulates the oxidative phosphorylation machinery via mitochondrial fission. Proc Natl Acad Sci U S A. 2011;108:12920-4 pubmed publisher..We found that the bioenergetic defects in the Pink1-KO can be ameliorated by expression of Drp1, a key molecule in mitochondrial fission...
- Ratnaparkhi A. Signaling by Folded gastrulation is modulated by mitochondrial fusion and fission. J Cell Sci. 2013;126:5369-76 pubmed publisher..The findings presented here show that mitochondria, through regulation of fusion and fission, function as downstream effectors and modulators of Fog signaling and Fog-dependent cell shape change. ..
- Huang Z, Ren S, Jiang Y, Wang T. PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila. Cell Death Dis. 2016;7:e2179 pubmed publisher..In addition, the results demonstrated that maintaining mitochondrial homeostasis via PINK1/Parkin-dependent mitochondrial quality control can potentially alleviate cell death in a wide range of neurodegenerative diseases. ..
- Hollenbeck P. Mitochondria and neurotransmission: evacuating the synapse. Neuron. 2005;47:331-3 pubmed..Now, evidence from the nervous system of Drosophila identifies the specific subcellular events that are most dependent upon nearby mitochondria. ..
- Parker D, Iyer A, Shah S, Morán A, Hjelmeland A, Basu M, et al. A new mitochondrial pool of cyclin E, regulated by Drp1, is linked to cell-density-dependent cell proliferation. J Cell Sci. 2015;128:4171-82 pubmed publisher..Loss of the mitochondrial fission protein dynamin-related protein 1 (Drp1, SwissProt O00429 in humans) augments mitochondrial respiration and elevates the mtCycE pool allowing CycE ..
- Wiemerslage L, Lee D. Quantification of mitochondrial morphology in neurites of dopaminergic neurons using multiple parameters. J Neurosci Methods. 2016;262:56-65 pubmed publisher..We suggest at least four variables should be considered when using mitochondrial structure as an experimental endpoint. ..
- Tanner E, Blute T, Brachmann C, McCall K. Bcl-2 proteins and autophagy regulate mitochondrial dynamics during programmed cell death in the Drosophila ovary. Development. 2011;138:327-38 pubmed publisher..Furthermore, Bcl-2 family mutants show a striking defect in cell death in the ovary. These data indicate that a mitochondrial pathway is a major mechanism for activation of cell death in Drosophila oogenesis. ..
- Zhu M, Li X, Tian X, Wu C. Mask loss-of-function rescues mitochondrial impairment and muscle degeneration of Drosophila pink1 and parkin mutants. Hum Mol Genet. 2015;24:3272-85 pubmed publisher..Together, our data strongly suggest that Mask/ANKHD1 activity can be inhibited in a tissue- and timely-controlled fashion to restore mitochondrial integrity under PD-linked pathological conditions. ..
- Sandoval H, Yao C, Chen K, Jaiswal M, Donti T, Lin Y, et al. Mitochondrial fusion but not fission regulates larval growth and synaptic development through steroid hormone production. elife. 2014;3: pubmed publisher..Marf mutants also fail to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fission mutants. However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan...
- Khalil B, El Fissi N, Aouane A, Cabirol Pol M, Rival T, LiÃ©vens J. PINK1-induced mitophagy promotes neuroprotection in Huntington's disease. Cell Death Dis. 2015;6:e1617 pubmed publisher..Altogether, our findings suggest that mitophagy is altered in the presence of mHtt and that increasing PINK1/Parkin mitochondrial quality control pathway may improve mitochondrial integrity and neuroprotection in HD. ..
- Zhang Y, Liu X, Bai J, Tian X, Zhao X, Liu W, et al. Mitoguardin Regulates Mitochondrial Fusion through MitoPLD and Is Required for Neuronal Homeostasis. Mol Cell. 2016;61:111-24 pubmed publisher..Therefore, we propose that MIGA proteins promote mitochondrial fusion by regulating mitochondrial phospholipid metabolism via MitoPLD. ..
- Chin Y, Lee A, Kan H, Laiman J, Chuang M, Hsieh S, et al. Dynamin-2 mutations associated with centronuclear myopathy are hypermorphic and lead to T-tubule fragmentation. Hum Mol Genet. 2015;24:5542-54 pubmed publisher..Our results demonstrate that CNM-Dyn2 mutants are gain-of-function mutations, and their primary effect in muscle is T-tubule disorganization, which explains the susceptibility of muscle to Dyn2 hyperactivity. ..
- Muliyil S, Narasimha M. Mitochondrial ROS regulates cytoskeletal and mitochondrial remodeling to tune cell and tissue dynamics in a model for wound healing. Dev Cell. 2014;28:239-52 pubmed publisher..They identify a pathway triggered by ROS and mediated by the Rho effector ROCK and its substrates that influences tissue patterning and homeostasis through the coordinate regulation of both mitochondrial morphology and tissue tension. ..
- Vos M, Lovisa B, Geens A, Morais V, Wagnieres G, van den Bergh H, et al. Near-infrared 808 nm light boosts complex IV-dependent respiration and rescues a Parkinson-related pink1 model. PLoS ONE. 2013;8:e78562 pubmed publisher..Thus, our data indicate that improvement of mitochondrial function using infrared light stimulation is a viable strategy to alleviate pink1-related defects. ..
- Bergstrom D, Merli C, Cygan J, Shelby R, Blackman R. Regulatory autonomy and molecular characterization of the Drosophila out at first gene. Genetics. 1995;139:1331-46 pubmed..Last, we discuss our data in light of the observation that the enhancers controlling dpp expression in the imaginal disks have no effect on the relatively nearby oaf gene...
- Abdelwahid E, Yokokura T, Krieser R, Balasundaram S, Fowle W, White K. Mitochondrial disruption in Drosophila apoptosis. Dev Cell. 2007;12:793-806 pubmed..The dynamin-related protein, Drp1, is important for Reaper- and DNA-damage-induced mitochondrial disruption...
- Spencer F, Hoffmann F, Gelbart W. Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. Cell. 1982;28:451-61 pubmed..Many structural similarities exist between the decapentaplegic and bithorax gene complexes. ..
- van der Bliek A. Functional diversity in the dynamin family. Trends Cell Biol. 1999;9:96-102 pubmed..This article describes current understanding of the structure and function of the various dynamin family members. ..
- Burman J, Yu S, Poole A, Decal R, Pallanck L. Analysis of neural subtypes reveals selective mitochondrial dysfunction in dopaminergic neurons from parkin mutants. Proc Natl Acad Sci U S A. 2012;109:10438-43 pubmed publisher..Moreover, our neural purification method provides a foundation to further explore the pathogenesis of Parkinson disease, and to address other neurobiological questions requiring the analysis of defined neural cell types. ..
- Gupte T. Mitochondrial Fragmentation Due to Inhibition of Fusion Increases Cyclin B through Mitochondrial Superoxide Radicals. PLoS ONE. 2015;10:e0126829 pubmed publisher..Our results provide an insight into the need for mitofusin-degradation during mitosis and also help in understanding the mechanism by which mitofusins may function as tumor suppressors. ..
- Lv F, Yang X, Cui C, Su C. Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the A?42 transgenic Drosophila model. PLoS ONE. 2017;12:e0176183 pubmed publisher..Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's ..
- Rikhy R, Kamat S, Ramagiri S, Sriram V, Krishnan K. Mutations in dynamin-related protein result in gross changes in mitochondrial morphology and affect synaptic vesicle recycling at the Drosophila neuromuscular junction. Genes Brain Behav. 2007;6:42-53 pubmed..Dynamin-related protein (DRP) is involved in the fission of mitochondria and peroxisomes...
- Muliyil S, Krishnakumar P, Narasimha M. Spatial, temporal and molecular hierarchies in the link between death, delamination and dorsal closure. Development. 2011;138:3043-54 pubmed publisher..They highlight the importance of mitochondrial dynamics and tissue mechanics in its regulation. Together, they provide novel insights into how apoptotic signals can be deployed to pattern tissues. ..
- Rival T, Macchi M, Arnauné Pelloquin L, Poidevin M, Maillet F, Richard F, et al. Inner-membrane proteins PMI/TMEM11 regulate mitochondrial morphogenesis independently of the DRP1/MFN fission/fusion pathways. EMBO Rep. 2011;12:223-30 pubmed publisher..are required for outer- and inner-mitochondrial membrane fusion respectively whereas dynamin-related protein 1 (DRP1) is the master regulator of mitochondrial fission...
- Yun J, Puri R, Yang H, Lizzio M, Wu C, Sheng Z, et al. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. elife. 2014;3:e01958 pubmed publisher..The MUL1 pathway compensates for loss of PINK1/parkin in both Drosophila and mammals and is a promising therapeutic target for PD.DOI: http://dx.doi.org/10.7554/eLife.01958.001. ..
- Chao Y, Robak L, Xia F, Koenig M, Adesina A, Bacino C, et al. Missense variants in the middle domain of DNM1L in cases of infantile encephalopathy alter peroxisomes and mitochondria when assayed in Drosophila. Hum Mol Genet. 2016;25:1846-56 pubmed publisher..We find that human wild-type DNM1L rescues the lethality as well as specific phenotypes associated with the loss of Drp1 in Drosophila. Neither the p.A395D variant nor the novel variant p.G350R rescue lethality or other phenotypes...
- Fowler P, O Sullivan N. ER-shaping proteins are required for ER and mitochondrial network organization in motor neurons. Hum Mol Genet. 2016;25:2827-2837 pubmed..Furthermore, genetically increasing mitochondrial fission, by overexpression of dynamin-related protein 1 (Drp1), restores mitochondrial network organization and rescues locomotor deficits in two independent Drosophila models ..
- DUBOFF B, Götz J, Feany M. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron. 2012;75:618-32 pubmed publisher..mitochondrial fission and show that excess actin stabilization inhibits association of the fission protein DRP1 with mitochondria, leading to mitochondrial elongation and subsequent neurotoxicity...
- Mitra K, Rikhy R, Lilly M, Lippincott Schwartz J. DRP1-dependent mitochondrial fission initiates follicle cell differentiation during Drosophila oogenesis. J Cell Biol. 2012;197:487-97 pubmed publisher..cell layer of developing ovarioles with down-regulated expression of the major mitochondrial fission protein DRP1 had mitochondrial elements extensively fused instead of being dispersed. These cells did not exit the cell cycle...
- Kjaerulff O, Verstreken P, Bellen H. Synaptic vesicle retrieval: still time for a kiss. Nat Cell Biol. 2002;4:E245-8 pubmed
- Chouhan A, Zhang J, Zinsmaier K, MacLeod G. Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ. J Neurosci. 2010;30:1869-81 pubmed publisher..Our findings indicate that presynaptic mitochondria have a similar affinity for Ca(2+) in functionally different nerve terminals, but do not limit cytosolic Ca(2+) levels within the range of motor neuron firing rates in situ. ..
- Banerjee S, Chinthapalli B. A proteomic screen with Drosophila Opa1-like identifies Hsc70-5/Mortalin as a regulator of mitochondrial morphology and cellular homeostasis. Int J Biochem Cell Biol. 2014;54:36-48 pubmed publisher..Taken together, we have identified a novel interaction between Hsc70-5/Mortalin and Opa1-like that influences cellular homeostasis through mitochondrial fusion. ..
- Vidal O, Stec W, Bausek N, Smythe E, Zeidler M. Negative regulation of Drosophila JAK-STAT signalling by endocytic trafficking. J Cell Sci. 2010;123:3457-66 pubmed publisher..As such, disruption in endocytic trafficking represents a potent negative regulator of the disease relevant JAK-STAT signalling cascade. ..
- Humphrey D, Parsons R, Ludlow Z, Riemensperger T, Esposito G, Verstreken P, et al. Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila. Hum Mol Genet. 2012;21:2698-712 pubmed publisher..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...
- Lee K, Wu Z, Song Y, Mitra S, Feroze A, Cheshier S, et al. Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes Dev. 2013;27:2642-7 pubmed publisher..Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling. ..
- Littleton J, Bellen H. Genetic and phenotypic analysis of thirteen essential genes in cytological interval 22F1-2; 23B1-2 reveals novel genes required for neural development in Drosophila. Genetics. 1994;138:111-23 pubmed..Given that the average number of alleles per complementation group is greater than seven, it is very likely that all essential genes within this cytological interval have been identified. ..
- Fernandes C, Rao Y. Genome-wide screen for modifiers of Parkinson's disease genes in Drosophila. Mol Brain. 2011;4:17 pubmed publisher..Among them, opa1 and drp1 have been previously implicated in the PD pathways, whereas debra (dbr), Pi3K21B and ?4GalNAcTA are novel PD-..
- Macchi M, El Fissi N, Tufi R, Bentobji M, Liévens J, Martins L, et al. The Drosophila inner-membrane protein PMI controls crista biogenesis and mitochondrial diameter. J Cell Sci. 2013;126:814-24 pubmed publisher..Since PMI and its human orthologue TMEM11 are regulators of mitochondrial morphology, our data suggest that, by controlling crista length, PMI influences mitochondrial diameter and tubular shape. ..
- Bhandari P, Song M, Dorn G. Dissociation of mitochondrial from sarcoplasmic reticular stress in Drosophila cardiomyopathy induced by molecularly distinct mitochondrial fusion defects. J Mol Cell Cardiol. 2015;80:71-80 pubmed publisher..Here we compared heart tube function in three models of mitochondrial fragmentation in Drosophila cardiomyocytes: Drp1 expression, Opa1 RNAi, and mitofusin MARF RNA1...
- Vrailas Mortimer A, Del Rivero T, Mukherjee S, Nag S, Gaitanidis A, Kadas D, et al. A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila. Dev Cell. 2011;21:783-95 pubmed publisher..We propose that potentiating p38K might be instrumental in restoring the mitochondrial detoxification machinery and combating stress-induced aging. ..
- Rana A, Oliveira M, Khamoui A, Aparicio R, Rera M, Rossiter H, et al. Promoting Drp1-mediated mitochondrial fission in midlife prolongs healthy lifespan of Drosophila melanogaster. Nat Commun. 2017;8:448 pubmed publisher..Here, we show that upregulating Drp1-a Dynamin-related protein that promotes mitochondrial fission-in midlife, prolongs Drosophila lifespan and ..
- Clavier A, Ruby V, Rincheval Arnold A, Mignotte B, GuÃ©nal I. The Drosophila retinoblastoma protein, Rbf1, induces a Debcl- and Drp1-dependent mitochondrial apoptosis. J Cell Sci. 2015;128:3239-49 pubmed publisher..Here, we demonstrate that Debcl and the pro-fission gene Drp1 are necessary downstream of Buffy to trigger a mitochondrial fragmentation during Rbf1-induced apoptosis...