ACSF3 and Mal(onate)-Adapted Mitochondria David B. Lombard, Yingming Zhao  Cell Chemical Biology  Volume 24, Issue 6, Pages 649-650 (June 2017) DOI: 10.1016/j.chembiol.2017.06.004 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Proposed Malonate-Malonyl-CoA Cycle In mitochondria, high malonate levels inhibit the citric acid cycle enzyme succinate dehydrogenase (SDH). In the mitochondrial matrix, malonate can be converted into malonyl-CoA by ACSF3. Malonyl-CoA can be consumed, either by incorporation into protein lysine malonylation (Kmal) or by conversion into acetyl-CoA by malonyl-CoA decarboxylase (MCD). Cytosolic malonyl-CoA levels are regulated by the opposing actions of acetyl-CoA carboxylases (ACCs), which synthesize malonyl-CoA from acetyl-CoA and MCD. Malonyl-CoA can be used for synthesis of long-chain fatty acids (LCFAs). Malonyl-CoA inhibits fatty acid oxidation by suppressing carnitine palmitoyltransferase I (CPT1) activity. Alternatively, cytosolic malonyl-CoA can be incorporated into protein Kmal. Malonate and citrate can both freely travel between mitochondria, cytosol, and nucleus. Cytosolic citrate can be converted into acetyl-CoA, an intermediate in fatty acid synthesis. Putative enzyme(s) responsible for ligating malonate to form malonyl-CoA in the cytosol and nucleus remain unknown. ACLY, ATP citrate lyase; ACS, acyl-CoA synthetase; FAS, fatty acid synthase; PDH, pyruvate dehydrogenase; complex I, SDH, III, and IV represent mitochondrial respiration chain complexes. Cell Chemical Biology 2017 24, 649-650DOI: (10.1016/j.chembiol.2017.06.004) Copyright © 2017 Elsevier Ltd Terms and Conditions