PT  - JOURNAL ARTICLE
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
TI  - Inhibition of the deubiquitinase USP8 corrects a Drosophila PINK1 model of mitochondria dysfunction
AID  - 10.26508/lsa.201900392
DP  - 2019 Apr 01
TA  - Life Science Alliance
PG  - e201900392
VI  - 2
IP  - 2
4099  - https://www.life-science-alliance.org/content/2/2/e201900392.short
4100  - https://www.life-science-alliance.org/content/2/2/e201900392.full
SO  - Life Sci. Alliance2019 Apr 01; 2
AB  - 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.