Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy.

ABSTRACT: Acetyl-coenzyme A (AcCoA) sits at the nexus of nutrient metabolism and shuttles between the canonical and non-canonical tricarboxylic acid cycle^1,2, which is dynamically regulated by nutritional status, such as fasting³. Here we find that mitophagy is triggered after a reduction in cytosolic AcCoA levels through short-term fasting and through inhibition of ATP-citrate lyase (encoded by ACLY), mitochondrial citrate/malate antiporter (encoded by SLC25A1) or acyl-CoA synthetase short chain family member 2 (encoded by ACSS2), and the mitophagy can be counteracted by acetate supplementation. Notably, NOD-like receptor (NLR) family member X1 (NLRX1) mediates this effect. Disrupting NLRX1 abolishes cytosolic AcCoA reduction-induced mitophagy both in vitro and in vivo. Mechan

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12823391 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature