SUMO-2/3 modification of PINK1 restrains basal mitophagy through MAPL-dependent regulation of mitochondrial surveillance

The mitochondrial kinase PTEN-induced kinase 1 (PINK1) initiates mitophagy in response to mitochondrial damage, yet mechanisms that constrain its activation under basal conditions remain incompletely defined. Here, we identify a non-canonical SUMO-2/3 modification of PINK1 that suppresses basal mitophagy. We show that the mitochondrial E3 ligase mitochondrial-anchored protein ligase (MAPL/MUL1) promotes PINK1 SUMO-2/3 modification, while MAPL depletion reduces SUMOylation and enhances basal mitophagy. Targeted deSUMOylation increases PINK1 stabilisation and augments mitophagy. These findings reveal a novel SUMO-based checkpoint for basal PINK1 activation and mitochondrial quality control.