In addition to fatty acid synthesis in the cytosol, mitochondria also have their own fatty acid synthesis (mtFASII). Mitochondrial fatty acid synthesis is essential for cellular respiration and mitochondrial biogenesis. A role as a mediator in intracellular signal transduction is also assumed, as the levels of bioactive lipids, such as lysophospholipids and sphingolipids, correlate with mtFASII.
In the first step of mtFASII, malonyl-CoA is formed from malonic acid by ACSF3. This occurs in tandem with a mitochondrial isoform of ACC1 (mtACC1), which can still provide malonyl-CoA from acetyl-CoA. The fatty acids, such as octanoyl-ACP (C8), which forms the starting substrate of lipoic acid biosynthesis, are formed via further intermediate steps and chain extensions. Through lipoic acid as a cofactor respectively the degree of lipoylation, mtFASII has an influence on mitochondrial enzyme complexes in energy metabolism, such as the pyruvate dehydrogenase complex, the α-ketoglutarate dehydrogenase complex, the BCKDH complex and the glycine cleavage system (GCS), among others.