GAK and PRKCD are positive regulators of PRKN-independent mitophagy

• DOI: 10.1038/s41467-021-26331-7
• Publication Date: 2021-10-20T13:30:18Z
• Authors: Michael J. Munson; Benan J. Mathai; Matthew Yoke Wui Ng; Laura Trachsel-Mo...; Laura R. de la Ba...; Sebastian W. Schultz; Yahyah Aman; Alf H. Lystad; Sakshi Singh; Sachin Singh; Jørgen Wesche; Evandro F. Fang; Anne Simonsen
• Keywords: ULK1

The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy remains elusive. Here, we have screened for regulators PRKN-independent using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as mitophagy, with both being dispensable PRKN-dependent starvation-induced autophagy. demonstrate that the activity GAK PRKCD are required efficient vitro, is present on mitochondria, facilitates recruitment ULK1/ATG13 to early autophagic structures. Importantly, vivo relevance kinases regulation basal mitophagy. Knockdown homologue (gakh-1) C. elegans knockout homologues zebrafish led significant inhibition highlighting evolutionary these regulation.