Lipoic acid metabolism and mitochondrial redox regulation

• Published in: The Journal of biological chemistry Vol. 293; no. 20; pp. 7522 - 7530
• Main Authors: Solmonson, Ashley, DeBerardinis, Ralph J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.05.2018; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; cell metabolism; Energy Metabolism; Humans; Lipid Metabolism; lipoic acid; mitochondria; Mitochondria - physiology; Oxidation-Reduction; oxidation-reduction (redox); redox regulation; Thematic Minireviews; Thioctic Acid - metabolism; tricarboxylic acid cycle (TCA cycle) (Krebs cycle); cell metabolism; tricarboxylic acid cycle (TCA cycle) (Krebs cycle); redox regulation; lipoic acid; mitochondria; oxidation-reduction (redox)
• ISSN: 0021-9258; 1083-351X; 1083-351X
• DOI: 10.1074/jbc.TM117.000259

Lipoic acid is an essential cofactor for mitochondrial metabolism and is synthesized de novo using intermediates from mitochondrial fatty-acid synthesis type II, S-adenosylmethionine and iron–sulfur clusters. This cofactor is required for catalysis by multiple mitochondrial 2-ketoacid dehydrogenase complexes, including pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and branched-chain ketoacid dehydrogenase. Lipoic acid also plays a critical role in stabilizing and regulating these multienzyme complexes. Many of these dehydrogenases are regulated by reactive oxygen species, mediated through the disulfide bond of the prosthetic lipoyl moiety. Collectively, its functions explain why lipoic acid is required for cell growth, mitochondrial activity, and coordination of fuel metabolism.