Ann Saada

Summary

Affiliation: Hadassah University Hospital
Country: Israel

Publications

  1. doi request reprint Mitochondria: mitochondrial OXPHOS (dys) function ex vivo--the use of primary fibroblasts
    Ann Saada
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel Department of Genetics and Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel Electronic address
    Int J Biochem Cell Biol 48:60-5. 2014
  2. pmc Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency
    Andreas Ohlenbusch
    Department of Pediatrics and Pediatric Neurology, Georg August University, Robert Koch Str, 40, Gottingen, 37075, Germany
    Orphanet J Rare Dis 7:69. 2012
  3. doi request reprint Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency
    Ann Saada
    Metabolic Disease Unit, Hadassah Medical Center, Jerusalem 91120, Israel
    Mol Genet Metab 95:169-73. 2008
  4. doi request reprint Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7
    Ann Saada
    Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel
    J Inherit Metab Dis 35:125-31. 2012
  5. doi request reprint The use of individual patient's fibroblasts in the search for personalized treatment of nuclear encoded OXPHOS diseases
    Ann Saada
    Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh, Hadassah Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel
    Mol Genet Metab 104:39-47. 2011
  6. pmc Screening for active small molecules in mitochondrial complex I deficient patient's fibroblasts, reveals AICAR as the most beneficial compound
    Anna Golubitzky
    Monique and Jacques Roboh Department of Genetic Research, Department of Genetics and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
    PLoS ONE 6:e26883. 2011
  7. pmc Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease
    Ann Saada
    Metabolic Disease Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Am J Hum Genet 84:718-27. 2009
  8. pmc Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia
    Simon Edvardson
    Metabolic Disease Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Am J Hum Genet 83:643-8. 2008
  9. ncbi request reprint Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
    Biochem Biophys Res Commun 310:963-6. 2003
  10. pmc C6ORF66 is an assembly factor of mitochondrial complex I
    Ann Saada
    Metabolic Disease Unit and, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Am J Hum Genet 82:32-8. 2008

Collaborators

Detail Information

Publications39

  1. doi request reprint Mitochondria: mitochondrial OXPHOS (dys) function ex vivo--the use of primary fibroblasts
    Ann Saada
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel Department of Genetics and Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel Electronic address
    Int J Biochem Cell Biol 48:60-5. 2014
    ..The usefulness of fibroblasts in culture to verify and study the pathomechanism of new mitochondrial diseases and to evaluate the efficacy of individual treatment options is summarized in this review. ..
  2. pmc Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency
    Andreas Ohlenbusch
    Department of Pediatrics and Pediatric Neurology, Georg August University, Robert Koch Str, 40, Gottingen, 37075, Germany
    Orphanet J Rare Dis 7:69. 2012
    ..Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype...
  3. doi request reprint Mitochondrial deoxyribonucleotide pools in deoxyguanosine kinase deficiency
    Ann Saada
    Metabolic Disease Unit, Hadassah Medical Center, Jerusalem 91120, Israel
    Mol Genet Metab 95:169-73. 2008
    ..It is suggested that the cytoplasmic deoxycytine kinase supplemented with external substrates may compensate for the deficient dGK...
  4. doi request reprint Combined OXPHOS complex I and IV defect, due to mutated complex I assembly factor C20ORF7
    Ann Saada
    Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel
    J Inherit Metab Dis 35:125-31. 2012
    ..Given the significant 1:290 carrier rate for the p.G250V mutation among Ashkenazi Jews, this mutation should be screened in all Ashkenazi patients with Leigh's syndrome prior to muscle biopsy...
  5. doi request reprint The use of individual patient's fibroblasts in the search for personalized treatment of nuclear encoded OXPHOS diseases
    Ann Saada
    Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh, Hadassah Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel
    Mol Genet Metab 104:39-47. 2011
    ..Examples and different approaches in the search for treatment options, while using fibroblasts from patients with nuclear encoded OXPHOS defects as model systems, are summarized and discussed...
  6. pmc Screening for active small molecules in mitochondrial complex I deficient patient's fibroblasts, reveals AICAR as the most beneficial compound
    Anna Golubitzky
    Monique and Jacques Roboh Department of Genetic Research, Department of Genetics and Metabolic Diseases, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
    PLoS ONE 6:e26883. 2011
    ....
  7. pmc Mutations in NDUFAF3 (C3ORF60), encoding an NDUFAF4 (C6ORF66)-interacting complex I assembly protein, cause fatal neonatal mitochondrial disease
    Ann Saada
    Metabolic Disease Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Am J Hum Genet 84:718-27. 2009
    ..These data not only show that NDUFAF3 mutations cause complex I deficiency but also relate different complex I disease genes by the close cooperation of their encoded proteins during the assembly process...
  8. pmc Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia
    Simon Edvardson
    Metabolic Disease Unit, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Am J Hum Genet 83:643-8. 2008
    ..In patients with autosomal-recessive unclassified leukodystrophy or complex spastic paraparesis, sequence analysis of the FA2H gene is warranted...
  9. ncbi request reprint Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
    Biochem Biophys Res Commun 310:963-6. 2003
    ..These findings underline the importance of balanced mitochondrial dNTP pools for mtDNA synthesis and may serve as the basis for future therapeutic interventions...
  10. pmc C6ORF66 is an assembly factor of mitochondrial complex I
    Ann Saada
    Metabolic Disease Unit and, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    Am J Hum Genet 82:32-8. 2008
    ..These data suggest that C6ORF66 is an assembly factor of complex I. Interestingly, the C6ORF66 gene product was previously shown to promote breast cancer cell invasiveness...
  11. doi request reprint Mitochondrial complex I deficiency caused by a deleterious NDUFA11 mutation
    Itai Berger
    Pediatric Neurology Unit, Hadassah Hebrew University Medical Center, Jerusalem
    Ann Neurol 63:405-8. 2008
    ..Mutation analysis of the NDUFA11 is warranted in isolated complex I deficiency presenting with infantile lactic acidemia or encephalocardiomyopathy...
  12. pmc Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion
    Orly Elpeleg
    Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
    Am J Hum Genet 76:1081-6. 2005
    ..Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase; hence, we propose that a defect in the last step of mitochondrial dNTP salvage is a novel cause of the mtDNA depletion syndrome...
  13. ncbi request reprint Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation
    Chaya Miller
    Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
    Ann Neurol 56:734-8. 2004
    ..A new group of mitochondrial respiratory chain disorders is proposed, resulting from mutations in nuclear encoded components of the mitochondrial translation apparatus...
  14. pmc Acute infantile liver failure due to mutations in the TRMU gene
    Avraham Zeharia
    Department of Human Genetics and Metabolic Diseases, Hadassah, The Hebrew University Medical Center, Jerusalem, Israel
    Am J Hum Genet 85:401-7. 2009
    ..Given that sulfur is a TRMU substrate and its availability is limited during the neonatal period, we propose that there is a window of time whereby patients with TRMU mutations are at increased risk of developing liver failure...
  15. doi request reprint Mitochondrial performance in heat acclimation--a lesson from ischemia/reperfusion and calcium overload insults in the heart
    Miri Assayag
    Laboratory of Environmental Physiology, Faculty of Dental Medicine, The Hebrew University, Jerusalem, Israel
    Am J Physiol Regul Integr Comp Physiol 303:R870-81. 2012
    ..LTHA was required for respiratory complex I adaptation and HACT. Stabilized higher basal [Ca2+]m and attenuated Ca2+ overload are likely connected to this adaptation...
  16. ncbi request reprint mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, Post Office Box 3235, IL 91031 Jerusalem, Israel
    Mol Genet Metab 79:1-5. 2003
    ..Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency...
  17. pmc 2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase
    Phyllis Dan
    Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Lipids Health Dis 10:84. 2011
    ....
  18. doi request reprint The effect of antiepileptic drugs on mitochondrial activity: a pilot study
    Itai Berger
    The Neuro Pediatric Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    J Child Neurol 25:541-5. 2010
    ....
  19. pmc Replacement of the C6ORF66 assembly factor (NDUFAF4) restores complex I activity in patient cells
    Dana Marcus
    Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel Canada IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel
    Mol Med 19:124-34. 2013
    ..Our results suggest that this approach of protein replacement therapy for the treatment of mitochondrial disorders is a promising one...
  20. doi request reprint Agenesis of corpus callosum and optic nerve hypoplasia due to mutations in SLC25A1 encoding the mitochondrial citrate transporter
    Simon Edvardson
    Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
    J Med Genet 50:240-5. 2013
    ..We now report the results of the biochemical and molecular studies of a patient with severe neurodevelopmental disease manifesting by agenesis of corpus callosum and optic nerve hypoplasia...
  21. pmc Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia
    Simon Edvardson
    Pediatric Neurology Unit, Hadassah Hebrew University Medical Center, Jerusalem, 91120, Israel
    Am J Hum Genet 81:857-62. 2007
    ..We speculate that missplicing mutations in mitochondrial aminoacyl-tRNA synthethase genes preferentially affect the brain because of a tissue-specific vulnerability of the splicing machinery...
  22. ncbi request reprint Evaluation of enzymatic assays and compounds affecting ATP production in mitochondrial respiratory chain complex I deficiency
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, POB 3235, Jerusalem 91031, Israel
    Anal Biochem 335:66-72. 2004
    ..The NADH-ferricyanide reductase assay play a helpful role in directing mutation analysis and identifying patients which are more likely to have their cells amenable for ATP production assessment...
  23. doi request reprint The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion
    Chaya Miller
    Department of Genetics and Metabolic Diseases, Hadassah Hebrew University Medical Center, POB 1200, 91120 Jerusalem, Israel
    Biochim Biophys Acta 1812:625-9. 2011
    ..Although results pertain to a cell culture system, the findings might explain the pathomechanism and tissue specificity in mtDNA depletion caused by defective SUCLA2...
  24. pmc alpha-Synuclein abnormalities in mouse models of peroxisome biogenesis disorders
    Eugenia Yakunin
    Department of Biochemistry and Molecular Biology, The Institute for Medical Research Israel Canada, Hebrew University, Jerusalem, Israel
    J Neurosci Res 88:866-76. 2010
    ..Furthermore, we show that alphaS abnormalities correlate with the altered lipid metabolism and, specifically, with accumulation of long chain, n-6 polyunsaturated fatty acids that occurs in the PBD models...
  25. pmc Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood
    Avraham Zeharia
    The Metabolic Disease Unit, Hadassah, Hebrew University Medical Center, Jerusalem 91120, Israel
    Am J Hum Genet 83:489-94. 2008
    ..Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy...
  26. doi request reprint Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing
    Itai Berger
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Mol Genet Metab 104:517-20. 2011
    ..In summary, linkage analysis followed by exome sequencing of a single patient is a cost-effective approach for the identification of disease causing mutations in small non-consanguineous families...
  27. pmc Exocrine pancreatic insufficiency, dyserythropoeitic anemia, and calvarial hyperostosis are caused by a mutation in the COX4I2 gene
    Eyal Shteyer
    The Metabolic Disease Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Am J Hum Genet 84:412-7. 2009
    ..Mutation analysis of COX4I2 is warranted in patients with malabsorption due to exocrine pancreatic insufficiency and in patients with dyserythropoeitic anemia...
  28. doi request reprint TAT-mediated delivery of LAD restores pyruvate dehydrogenase complex activity in the mitochondria of patients with LAD deficiency
    Matan Rapoport
    Department of Cellular Biochemistry and Human Genetics, Faculty of Medicine, Hebrew University, Jerusalem, Israel
    Mol Ther 16:691-7. 2008
    ..We believe that this approach involving TAT-mediated enzyme replacement therapy (ERT) can be applied to the treatment of LAD deficiency as well as to other mitochondrial and metabolic disorders...
  29. doi request reprint Rat cardiac mitochondrial sub-populations show distinct features of oxidative phosphorylation during ischemia, reperfusion and ischemic preconditioning
    Gino A Kurian
    Department of Cellular Biochemistry and Human Genetics, The Hebrew University Hadassah Schools of Medicine and Dental Medicine, Jerusalem, Israel
    Cell Physiol Biochem 30:83-94. 2012
    ..This study was undertaken to compare functional oxidative phosphorylation (OXPHOS) in IFM and SSM during ischemia, reperfusion and ischemic preconditioning...
  30. doi request reprint Human granulosa luteal cell oxidative phosphorylation function is not affected by age or ovarian response
    Yoel Shufaro
    IVF Unit, Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Fertil Steril 98:166-72. 2012
    ..To safely prepare a functional autologous mitochondrial concentrate (MC) from follicular fluid (FF) cells, and to determine the effect of age and ovarian response on the oxidative phosphorylation (OXPHOS)...
  31. pmc Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit
    Igor Ruvinsky
    Department of Biochemistry and Molecular Biology, IMRIC, Hebrew University Hadassah Medical School, Jerusalem, Israel
    PLoS ONE 4:e5618. 2009
    ..A relatively passive behavior of these mice has raised the possibility that they suffer from muscle weakness, which has, indeed, been confirmed by a variety of physical performance tests...
  32. doi request reprint l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation
    Simon Edvardson
    Pediatric Neurology Unit, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Mol Genet Metab 101:228-32. 2010
    ..Similarly, there was an apparent improvement in cognitive function, with significantly increased IQ-scores in the sister and marginal improvement in the brother...
  33. doi request reprint The effect of small molecules on nuclear-encoded translation diseases
    Devorah Soiferman
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel Department of Genetics and Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Biochimie 100:184-91. 2014
    ....
  34. doi request reprint Elevated plasma citrulline: look for dihydrolipoamide dehydrogenase deficiency
    Ruby Haviv
    Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
    Eur J Pediatr 173:243-5. 2014
    ..Interestingly, elevated plasma citrulline was associated with the common G229C mutation. In conclusion, we suggest that elevated plasma citrulline in the absence of urea cycle defects warrants an investigation for DLD deficiency. ..
  35. doi request reprint The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy
    Polina Stepensky
    Department of Pediatric Hematology Oncology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel
    Blood 121:5078-87. 2013
    ..This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure...
  36. ncbi request reprint Depletion of the other genome-mitochondrial DNA depletion syndromes in humans
    Orly Elpeleg
    Hebrew University, Faculty of Medicine, Jerusalem, Israel
    J Mol Med (Berl) 80:389-96. 2002
    ..We also speculate on future genes to be discovered in other phenotypes of mtDNA depletion...
  37. pmc The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition
    Virginie Loeb
    Department of Biochemistry and Molecular Biology, The Institute for Medical Research, Israel Canada, Hebrew University, Jerusalem 91120, Israel
    J Biol Chem 285:7334-43. 2010
    ..Based on the results herein, we suggest that alphaS expression negatively regulates complex I activity as part of its normal, physiological role...
  38. ncbi request reprint Deoxyribonucleotides and disorders of mitochondrial DNA integrity
    Ann Saada
    Metabolic Disease Unit, Shaare Zedek Medical Center, Jerusalem, Israel
    DNA Cell Biol 23:797-806. 2004
    ..This article reviews the current knowledge of deoxyribonucleotide metabolism in relation to disorders affecting mtDNA integrity...
  39. doi request reprint Ceramide and the mitochondrial respiratory chain
    Aviram Kogot-Levin
    Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center, Jerusalem, Israel Department of Genetics and Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel
    Biochimie 100:88-94. 2014
    ..The physiological significance of synthetic short and naturally occurring long chain ceramides in modulating mitochondrial function with emphasis on the MRC will be discussed. ..