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bioRxiv · 10.1101/2025.05.27.656300

PINK1 SUMOylation regulates basal mitophagy

Ramesh, N. S.·Seager, R.·Wilkinson, K.·Henley, J. M.
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Abstract

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.

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Ramesh, N. S., Seager, R., Wilkinson, K., Henley, J. M.. 2025-05-29. PINK1 SUMOylation regulates basal mitophagy. https://doi.org/10.1101/2025.05.27.656300

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