TY - JOUR T1 - Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900392 VL - 2 IS - 2 SP - e201900392 AU - Sophia von Stockum AU - Alvaro Sanchez-Martinez AU - Samantha Corrà AU - Joy Chakraborty AU - Elena Marchesan AU - Lisa Locatello AU - Caterina Da Rè AU - Paola Cusumano AU - Federico Caicci AU - Vanni Ferrari AU - Rodolfo Costa AU - Luigi Bubacco AU - Maria Berica Rasotto AU - Ildiko Szabo AU - Alexander J Whitworth AU - Luca Scorrano AU - Elena Ziviani Y1 - 2019/04/01 UR - https://www.life-science-alliance.org/content/2/2/e201900392.abstract N2 - 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. ER -