MCART1/SLC25A51 is required for mitochondrial NAD transport
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 phosp...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2021
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| Online Access: | https://hdl.handle.net/1721.1/135285 |
| _version_ | 1826206628383293440 |
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| author | 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 Lewis, Caroline A Sabatini, David M |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research 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 Lewis, Caroline A Sabatini, David M |
| author_sort | Kory, Nora |
| collection | MIT |
| description | 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. + + + + |
| first_indexed | 2024-09-23T13:36:05Z |
| format | Article |
| id | mit-1721.1/135285 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:36:05Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | dspace |
| spelling | mit-1721.1/1352852023-09-14T20:01:47Z MCART1/SLC25A51 is required for mitochondrial NAD transport 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 Lewis, Caroline A Sabatini, David M Whitehead Institute for Biomedical Research Howard Hughes Medical Institute Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT 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. + + + + 2021-10-27T20:22:48Z 2021-10-27T20:22:48Z 2020 2021-07-23T18:31:09Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135285 en 10.1126/SCIADV.ABE5310 Science Advances Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf American Association for the Advancement of Science (AAAS) Science Advances |
| spellingShingle | 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 Lewis, Caroline A Sabatini, David M MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title | MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title_full | MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title_fullStr | MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title_full_unstemmed | MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title_short | MCART1/SLC25A51 is required for mitochondrial NAD transport |
| title_sort | mcart1 slc25a51 is required for mitochondrial nad transport |
| url | https://hdl.handle.net/1721.1/135285 |
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