Segregation of pathways leading to pexophagy

Barone, Francesco G ORCID: 0000-0003-4382-9313, Urbe, Sylvie ORCID: 0000-0003-4735-9814 and Clague, Michael J ORCID: 0000-0003-3355-9479 (2023) Segregation of pathways leading to pexophagy. LIFE SCIENCE ALLIANCE, 6 (5). e202201825-.

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Abstract

Peroxisomes are organelles with key roles in metabolism including long-chain fatty acid production. Their metabolic functions overlap and interconnect with those of mitochondria, with which they share an overlapping but distinct proteome. Both organelles are degraded by selective autophagy processes termed pexophagy and mitophagy. Although mitophagy has received intense attention, the pathways linked to pexophagy and associated tools are less well developed. We have identified the neddylation inhibitor MLN4924 as a potent activator of pexophagy and show that this is mediated by the HIF1α-dependent up-regulation of BNIP3L/NIX, a known adaptor for mitophagy. We show that this pathway is distinct from pexophagy induced by the USP30 deubiquitylase inhibitor CMPD-39, for which we identify the adaptor NBR1 as a central player. Our work suggests a level of complexity to the regulation of peroxisome turnover that includes the capacity to coordinate with mitophagy, via NIX, which acts as a rheostat for both processes.

Item Type:	Article
Uncontrolled Keywords:	Peroxisomes, Autophagy, Macroautophagy, Mitophagy
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	06 Mar 2023 09:48
Last Modified:	23 Mar 2023 00:44
DOI:	10.26508/lsa.202201825
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3168780