Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism (By similarity). Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA (By similarity). Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (PubMed:24913514). Together with its cytosolic isozyme ACACA, which is involved in de novo fatty acid biosynthesis, promotes lipid storage (PubMed:24913514). acetyl-CoA + ATP + hydrogencarbonate = ADP + H(+) + malonyl-CoA + phosphate Binds 2 magnesium or manganese ions per subunit. Activity is increased by oligomerization of the protein into filaments that correspond to the most active form of the carboxylase. The oligomerization and the activity of the enzyme are inhibited by phosphorylation at Ser-212 (PubMed:24913514). Inhibited by its own product malonyl-CoA. Activation by MID1IP1 is citrate dependent. Lipid metabolism; malonyl-CoA biosynthesis; malonyl-CoA from acetyl-CoA: step 1/1. Monomer, homodimer, and homotetramer. Forms filamentous polymers. Interacts with MID1IP1; interaction with MID1IP1 promotes oligomerization and increases its activity in a citrate-dependent manner. Up-regulated by endocannabinoid anandamide/AEA. Consists of an N-terminal biotin carboxylation/carboxylase (BC) domain that catalyzes the ATP-dependent transient carboxylation of the biotin covalently attached to the central biotinyl-binding/biotin carboxyl carrier (BCC) domain (By similarity). The C-terminal carboxyl transferase (CT) domain catalyzes the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA to produce malonyl-CoA (By similarity). The biotin cofactor is covalently attached to the central biotinyl-binding domain and is required for the catalytic activity. Phosphorylated by AMPK at Ser-212 inactivates the enzyme (PubMed:24913514). Required for the maintenance of skeletal muscle lipid and glucose homeostasis (PubMed:24913514). Normal morphology, fertility, growth rate and lifespan but higher than normal food consumption and fatty acid oxidation rate and decreased fat content in adipose tissue and liver (PubMed:11283375). A high-fat/high-carbohydrate diet results in maintenance of normal insulin and glucose levels with less weight gain and less fat accumulation than wild-type mice (PubMed:12920182). Elevated levels of Ucp2 in adipose tissue and heart but not in skeletal muscle or liver, and elevated levels of Ucp3 in skeletal muscle but not in heart or brown adipose tissue (PubMed:12920182). Significant decrease in body weight, weight of epidydimal fat pads and levels of hepatic triglycerides under a range of dietary conditions including normal chow diet, fasting and refeeding a fat-free high-carbohydrate diet, and a high-fat/high-carbohydrate diet (PubMed:22362781). Up-regulation of lipogenic enzymes under de novo lipogenic conditions but reduced fat accumulation in liver (PubMed:22362781). Primary cultured adipocytes show increased fatty acid and glucose oxidation rates and increased lipolysis (PubMed:15677334). Reduced heart size, reduced Mlycd and malonyl-CoA levels in mutant hearts, reduced myocardial triglyceride levels, higher myocardial oleate and glucose oxidation rates, reduced levels of Ppara and reduced activation of Mtor (PubMed:18487439, PubMed:22730442). However, it has also been reported that mutants show no differences in body weight, food intake, body composition or glucose homeostasis as compared with controls fed on chow or a high-fat diet (PubMed:20368432).