TY - JOUR
T1 - Lipoic acid metabolism and mitochondrial redox regulation
AU - Solmonson, Ashley
AU - DeBerardinis, Ralph J.
N1 - Funding Information:
This work was supported by National Institutes of Health Grant R35 CA220449 (to R. J. D.), the Howard Hughes Medical Institute (Faculty Scholars Pro-gram), and by a gift from the Once Upon a Time Foundation. This is the fifth article in the Thematic Minireview Series “Redox metabolism and signal-ing.” The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2018/5/18
Y1 - 2018/5/18
N2 - 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, -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.
AB - 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, -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.
UR - http://www.scopus.com/inward/record.url?scp=85046724624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046724624&partnerID=8YFLogxK
U2 - 10.1074/jbc.TM117.000259
DO - 10.1074/jbc.TM117.000259
M3 - Review article
C2 - 29191830
AN - SCOPUS:85046724624
SN - 0021-9258
VL - 293
SP - 7522
EP - 7530
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 20
ER -