MCART1/SLC25A51 is required for mitochondrial NAD transport.

Autor:	Kory N; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA.; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA., Uit de Bos J; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., van der Rijt S; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Jankovic N; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Güra M; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Arp N; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Pena IA; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Prakash G; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Chan SH; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Kunchok T; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Lewis CA; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA., Sabatini DM; Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA 02142, USA. sabatini@wi.mit.edu.; Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Department of Biology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.; Broad Institute of Harvard and Massachusetts Institute of Technology, 415 Main Street, Cambridge MA 02142, USA.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2020 Oct 21; Vol. 6 (43). Date of Electronic Publication: 2020 Oct 21 (Print Publication: 2020).
DOI:	10.1126/sciadv.abe5310
Abstrakt:	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. (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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