Proteomics

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GAK and PRKCD are positive regulators of Parkin-independent mitophagy


ABSTRACT: Mitophagy plays a key cellular role for the programmed or damage induced removal of mitochondria, however, precisely how this process is orchestrated in response to different stimuli still requires investigation. In this work we have screened for regulators of PARKIN-independent mitophagy using an siRNA library targeting 200 proteins containing lipid interacting domains. We identify Cyclin-G associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as novel regulators of PARKIN independent mitophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagy in vitro, that PRKCD is present on mitochondria, and that PRKCD is required for ULK1/ATG13 recruitment to early autophagic structures. Importantly, we demonstrate in vivo relevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) in C.elegans or PRKCD homologues in zebrafish led to significant inhibition of mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sachin Singh  

LAB HEAD: Anne Simonsen

PROVIDER: PXD022773 | Pride | 2021-09-29

REPOSITORIES: pride

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