USP30 Protein, Human (sf9, His)

USP30 Protein, anchored to the mitochondrial outer membrane, assumes a critical role as a deubiquitinating enzyme that acts as a key inhibitor of mitophagy, countering the actions of parkin (PRKN). By hydrolyzing ubiquitin attached by parkin on target proteins such as RHOT1/MIRO1 and TOMM20, USP30 impedes parkin's ability to drive mitophagy, thereby regulating the selective clearance of damaged mitochondria. Its substrate specificity extends to the preferential cleavage of 'Lys-6'- and 'Lys-11'-linked polyubiquitin chains, key linkages involved in mitophagic signaling. Notably, USP30 does not efficiently cleave polyubiquitin phosphorylated at 'Ser-65'. Beyond its role in mitophagy, USP30 also functions as a negative regulator of mitochondrial fusion, mediating the deubiquitination of MFN1 and MFN2. This dual role underscores the intricate regulatory mechanisms by which USP30 orchestrates mitochondrial dynamics and quality control, playing a central role in maintaining mitochondrial homeostasis.