Ubiquitin Specific Peptidase 30 (USP30)

USP30 is anchored to the mitochondrial outer membrane. Deletion and mutagenesis analyses showed that the N-terminal transmembrane domain and the positively charged residues in the C-terminal flanking region are required for the targeting and insertion of USP30 into the mitochondrial membrane. Depletion of USP30 expression by RNA interference induced elongated and interconnected mitochondria, depending on the activities of mitochondrial fusion factors, e.g., Fis1 and Drp1, without changing the expression levels of the key regulators for mitochondrial dynamics. Mitochondria were rescued from this abnormal phenotype by ectopic expression of USP30 in a manner dependent on its enzymatic activity. Overexpression of USP30 had no discernible effect on mitochondrial morphology.