Researchers at Fudan University discovered that cytosolic acetyl-coenzyme A (AcCoA) acts as a direct metabolic signal to control mitophagy — the cellular process of clearing damaged mitochondria. When AcCoA levels drop in the cytosol (as during fasting or when key enzymes like ACLY or SLC25A1 are inhibited), a mitochondrial outer membrane protein called NLRX1 detects the change and triggers mitochondrial removal. This mechanism operates independently of the two classic autophagy regulators AMPK and mTOR. Importantly, supplementing with acetate — which replenishes cytosolic AcCoA — blocked the mitophagy response. The same pathway was found to drive resistance to KRAS-targeted cancer drugs, making it a potentially actionable target for both longevity medicine and oncology.
