Extended Data Fig. 10: UCP1-independent thermogenesis through an ATP-consuming cycle of monomethyl branched chain fatty acid (mmBCFA) synthesis and β-oxidation.
From: Peroxisomal metabolism of branched fatty acids regulates energy homeostasis
Mitochondrial catabolism of branched chain amino acids (BCAA) generates a short-branched acylCoA (BrCoA), such as isovaleryl-CoA. Carnitine acetyltransferase (CRAT), which is localized in mitochondria and peroxisomes, catalyses interconversion of branched-chain acylcarnitine and BrCoA, which is exported to the cytosol. The de novo lipogenesis enzyme FASN translocates to peroxisomes in response to acute cold exposure or β-adrenergic receptor stimulation and mediates synthesis of mmBCFA using BrCoA as a precursor. ACOX2 promotes β-oxidation of mmBCFA, generating heat in the process. Activation of the FASN–ACOX2 thermogenic pathway depletes ATP, triggering AMPK activation to promote compensatory ATP synthesis and sustain thermogenesis. Graphic created using BioRender (https://biorender.com).
