PT  - JOURNAL ARTICLE
AU  - Vinh Dang Do
AU  - Nikhil Kumar Tulsian
AU  - Warren KY Tan
AU  - Zhe Li
AU  - Liyi Cheng
AU  - Matias I. Autio
AU  - Wilson LW Tan
AU  - Zenia Tiang
AU  - Arnaud Perrin
AU  - Jianhong Ching
AU  - Mayin Lee
AU  - Isabelle Bonne
AU  - Chrishan Ramachandra
AU  - Choon Kiat Lim
AU  - Derek J Hausenloy
AU  - Chester Lee Drum
AU  - A. Mark Richards
AU  - Ganesh S. Anand
AU  - Roger SY Foo
TI  - The novel conserved NAD<sup>+</sup>-binding micropeptide SGHRT regulates mitochondrial function and metabolism in human cardiomyocytes
AID  - 10.1101/2021.10.24.465637
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.10.24.465637
4099  - http://biorxiv.org/content/early/2021/10/26/2021.10.24.465637.short
4100  - http://biorxiv.org/content/early/2021/10/26/2021.10.24.465637.full
AB  - Nicotinamide 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.Competing Interest StatementThe authors have declared no competing interest.