1. The novel conserved NAD+-binding micropeptide SGHRT regulates mitochondrial function and metabolism in human cardiomyocytes
- Author
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Roger Foo, Liyi Cheng, A. Mark Richards, Warren Ky Tan, Matias I. Autio, Vinh Dang Do, Arnaud Perrin, Chester L. Drum, Zenia Tiang, Nikhil Kumar Tulsian, Chrishan J A Ramachandra, Ganesh S. Anand, Zhe Li, Isabelle Bonne, Jianhong Ching, Wilson Lw Tan, Choon Kiat Lim, Derek J. Hausenloy, and Mayin Lee
- Subjects
Flavin adenine dinucleotide ,Citric acid cycle ,NAD binding ,chemistry.chemical_compound ,Biochemistry ,chemistry ,biology ,biology.protein ,NAD+ kinase ,Mitochondrion ,Nicotinamide adenine dinucleotide ,Inner mitochondrial membrane ,Cofactor - Abstract
sNicotinamide adenine dinucleotide (NAD) is a critical metabolite and coenzyme for multiple metabolic pathways and cellular processes (1-4). In this study, we identified Singheart, SGHRT as a nuclear genome-encoded NAD+-binding mitochondrial micropeptide. SGHRT, present in both monomeric and dimeric forms, binds directly to NAD, but not NADH or flavin adenine dinucleotide (FAD). Localized to the inner mitochondrial membrane and mitochondrial matrix, SGHRT interacts with the mitochondrial enzymes Succinate-CoA Ligase and Succinate Dehydrogenase. SGHRT deletion in human embryonic stem cell derived cardiomyocytes disrupted mitochondria morphology, decreased total NAD and ATP abundance, and resulted in defective TCA cycle metabolism, the electron transport chain and in Ox-Phos processes. These results comprise the first report of an NAD+-binding micropeptide, SGHRT, required for mitochondrial function and metabolism.
- Published
- 2021
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