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Opposing roles for AMPK in regulating distinct mitophagy pathways

ABSTRACT: Mitophagy degrades damaged mitochondria, but we show here that it can also target functional mitochondria. This latter scenario occurs during programmed mitophagy and involves the mitophagy receptors NIX and BNIP3. While AMPK, the energy-sensing protein kinase, can influence damaged-induced mitophagy, its role in programmed mitophagy is unclear. We found that AMPK directly inhibits NIX-dependent mitophagy by triggering 14-3-3-mediated sequestration of ULK1, via ULK1 phosphorylation at two sites: Ser556 and an additional identified site, Ser694. In contrast, AMPK activation increases Parkin phosphorylation and enhances the rate of depolarisation-induced mitophagy, independently of ULK1. We show that this happens both in cultured cells and tissues in vivo, using the mito-QC mouse model. Our work unveils a mechanism whereby AMPK activation downregulates mitophagy of functional mitochondria but enhances that of dysfunctional/damaged ones.

INSTRUMENT(S): LTQ Orbitrap Velos, Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Conventional Osteosarcoma

SUBMITTER: Renata Soares

LAB HEAD: Ian G. Ganley

PROVIDER: PXD056956 | Pride | 2024-11-29

REPOSITORIES: Pride

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			Action	DRS
	ABishnu_240409_01.raw	Raw
	ABishnu_240409_02.raw	Raw
	ABishnu_240409_03.raw	Raw
	AMPKParkin.dat	Other
	AMPKParkin.mgf	Mgf

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