MCART1/SLC25A51 is required for mitochondrial NAD transport
Name
eabe5310.full.pdf
Description
Published version
Size
4.62 MB
Format
Adobe PDF
Checksum (MD5)
3d5c14af7a62eb8eb9d44875281af0d5
Author(s)
Kory, Nora
uit de Bos, Jelmi
van der Rijt, Sanne
Jankovic, Nevena
Güra, Miriam
Arp, Nicholas
Pena, Izabella A
Prakash, Gyan
Chan, Sze Ham
Kunchok, Tenzin
Date Issued
2020
Journal
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Version
Final published version
Abstract
The nicotinamide adenine dinucleotide (NAD /NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to adenosine triphosphate generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD transporter has been identified in yeast, how NAD enters mitochondria in metazoans is unknown. Here, we mine gene essentiality data from human cell lines to identify MCART1 (SLC25A51) as coessential with ETC components. MCART1-null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD and NADH. Isolated mitochondria from cells lacking or overexpressing MCART1 have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, MCART1 and NDT1, a yeast mitochondrial NAD transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells. + + + +
MIT Department
Whitehead Institute for Biomedical Research
Howard Hughes Medical Institute
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/SCIADV.ABE5310
