Catalyzes the conversion of malonyl-CoA to acetyl-CoA. In the fatty acid biosynthesis MCD selectively removes malonyl-CoA and thus assures that methyl-malonyl-CoA is the only chain elongating substrate for fatty acid synthase and that fatty acids with multiple methyl side chains are produced. In peroxisomes it may be involved in degrading intraperoxisomal malonyl-CoA, which is generated by the peroxisomal beta-oxidation of odd chain-length dicarboxylic fatty acids. Plays a role in the metabolic balance between glucose and lipid oxidation in muscle independent of alterations in insulin signaling. May play a role in controlling the extent of ischemic injury by promoting glucose oxidation. H(+) + malonyl-CoA = acetyl-CoA + CO2 Malonyl-CoA decarboxylase activity does not require any cofactors or divalent metal ions. Metabolic intermediate biosynthesis; acetyl-CoA biosynthesis; acetyl-CoA from malonyl-CoA: step 1/1. Homotetramer. Dimer of dimers. The two subunits within a dimer display conformational differences suggesting that at any given moment, only one of the two subunits is competent for malonyl-CoA binding and catalytic activity. Under oxidizing conditions, can form disulfide-linked homotetramers (in vitro). Associates with the peroxisomal targeting signal receptor PEX5 (By similarity). Enzymatically active in all three subcellular compartments. According to PubMed:10229677, a single transcription start site has been demonstrated. Expressed in liver, heart, skeletal muscles and adipose tissues (at protein level). Ubiquitous. Strongly expressed in liver, kidney, heart, skeletal muscle and adipose tissues. Weakly expressed in brain. Acetylation at Lys-471 activates malonyl-CoA decarboxylase activity. Deacetylation at Lys-471 by SIRT4 represses activity, leading to promote lipogenesis (By similarity). Interchain disulfide bonds may form in peroxisomes (Potential). Interchain disulfide bonds are not expected to form in the reducing environment of the cytoplasm and mitochondria. May be produced by alternative initiation at Met-39 of isoform mitochondrial. Alternatively, represents a proteolytic processed form of the mitochondrial form (PubMed:10947976).