USP30 is a deubiquitinating enzyme that associates with the mitochondrial outer membrane. RNAi depletion of USP30 induces elongated, interconnected mitochondria, suggesting that USP30 contributes to mitochondrial morphology (Nakamura & Hirose 2008).
Overexpression of USP30 removes ubiquitin attached to damaged mitochondria by PARK2 (Parkin), preventing PARK2-induced mitophagy, whereas reducing USP30 enhances mitochondrial degradation in neurons. Multiple mitochondrial substrates were found to be oppositely regulated by PARK2 and USP30. Knockdown of USP30 rescues defective mitophagy caused by pathogenic mutations in parkin and improves mitochondrial integrity in parkin- or Pink1-deficient flies. Knockdown of Usp30 in dopaminergic neurons protects flies against paraquat toxicity in vivo, ameliorating defects in dopamine levels, motor function, and organismal survival (Bingol et al. 2014).
thiol-dependent deubiquitinase activity of USP30:PolyUb-MOM proteins [mitochondrial outer membrane]