FBXL4 ubiquitin ligase deficiency promotes mitophagy by elevating NIX adaptor levels

ABSTRACT: Selective autophagy of mitochondria, mitophagy, is linked to mitochondrial quality control and as such critical to a healthy organism. We have used a CRISPR/Cas9 approach to screen human E3 ubiquitin ligases for influence on mitophagy under both basal cell culture conditions and upon acute mitochondrial depolarisation. We identify two cullin-RING ligase substrate receptors, VHL and FBXL4, as the most profound negative regulators of basal mitophagy. We show that these converge, albeit via different mechanisms, on control of the mitophagy adaptors BNIP3 and BNIP3L/NIX. FBXL4 restricts BNIP3 and NIX levels via direct interaction and protein destabilisation, while VHL acts through suppression of HIF1a-mediated transcription of BNIP3 and NIX. Depletion of NIX but not BNIP3 is sufficient to rest

SUBMITTER: Dr. Hannah Elcocks 

PROVIDER: S-SCDT-10_15252-EMBJ_2022112799 | biostudies-other |

REPOSITORIES: biostudies-other