期刊
LIFE SCIENCE ALLIANCE
卷 2, 期 2, 页码 -出版社
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.201900392
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资金
- Italian Ministry of Health Ricerca Finalizzata [GR-2011-02351151]
- Rita Levi Montalcini Brain Gain program
- Michael J Fox RRIA 2014 [9795]
- ERC [FP7-282280]
- FP7 CIG [PCIG13-GA-2013-618697]
- Italian Ministry of Research FIRB [RBAP11Z3YA_005]
- MRC Core funding [MC_UU_00015/6]
- Wellcome Trust [084757]
Aberrant mitochondrial dynamics disrupts mitochondrial function and contributes to disease conditions. A targeted RNA interference screen for deubiquitinating enzymes (DUBs) affecting protein levels of multifunctional mitochondrial fusion protein Mitofusin (MFN) identified USP8 prominently influencing MFN levels. Genetic and pharmacological inhibition of USP8 normalized the elevated MFN protein levels observed in PINK1 and Parkin-deficient models. This correlated with improved mitochondrial function, locomotor performance and life span, and prevented dopaminergic neurons loss in Drosophila PINK1 KO flies. We identified a novel target antagonizing pathologically elevated MFN levels, mitochondrial dysfunction, and dopaminergic neuron loss of a Drosophila model of mitochondrial dysfunction.
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