SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters
Abstract Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporte...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56402-y |
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| author | Mingyang Chen Luexiang Yuan Binxin Chen Hui Chang Jun Luo Hengbin Zhang Zhongjian Chen Jiao Kong Yaodong Yi Mengru Bai Minlei Dong Hui Zhou Huidi Jiang |
| author_facet | Mingyang Chen Luexiang Yuan Binxin Chen Hui Chang Jun Luo Hengbin Zhang Zhongjian Chen Jiao Kong Yaodong Yi Mengru Bai Minlei Dong Hui Zhou Huidi Jiang |
| author_sort | Mingyang Chen |
| collection | DOAJ |
| description | Abstract Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish nicotinamide metabolism homeostasis. In addition, ENT1/2 exhibits a strong capacity to change the cellular metabolite composition and the transcript, especially those related to nicotinamide. We further observe that ENT1/2 regulates cellular respiration and senescence, contributing by altering the NAD+ pool level and mitochondrial status. Changes to cellular respiration, mitochondrial status and senescence by ENT1/2 knockdown are reversed by NMN supplementation. Together, ENT1 and ENT2 act as both cellular nicotinamide-level keepers and nicotinamide biological regulators through their NAM transport functions. |
| format | Article |
| id | doaj-art-63da344f13f94fe996b829e5816d428e |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-63da344f13f94fe996b829e5816d428e2025-02-02T12:33:27ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-56402-ySLC29A1 and SLC29A2 are human nicotinamide cell membrane transportersMingyang Chen0Luexiang Yuan1Binxin Chen2Hui Chang3Jun Luo4Hengbin Zhang5Zhongjian Chen6Jiao Kong7Yaodong Yi8Mengru Bai9Minlei Dong10Hui Zhou11Huidi Jiang12College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityZhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, School of Medicine, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityZhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of SciencesCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityKey Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Westlake UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityCollege of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang UniversityAbstract Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish nicotinamide metabolism homeostasis. In addition, ENT1/2 exhibits a strong capacity to change the cellular metabolite composition and the transcript, especially those related to nicotinamide. We further observe that ENT1/2 regulates cellular respiration and senescence, contributing by altering the NAD+ pool level and mitochondrial status. Changes to cellular respiration, mitochondrial status and senescence by ENT1/2 knockdown are reversed by NMN supplementation. Together, ENT1 and ENT2 act as both cellular nicotinamide-level keepers and nicotinamide biological regulators through their NAM transport functions.https://doi.org/10.1038/s41467-025-56402-y |
| spellingShingle | Mingyang Chen Luexiang Yuan Binxin Chen Hui Chang Jun Luo Hengbin Zhang Zhongjian Chen Jiao Kong Yaodong Yi Mengru Bai Minlei Dong Hui Zhou Huidi Jiang SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters Nature Communications |
| title | SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters |
| title_full | SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters |
| title_fullStr | SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters |
| title_full_unstemmed | SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters |
| title_short | SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters |
| title_sort | slc29a1 and slc29a2 are human nicotinamide cell membrane transporters |
| url | https://doi.org/10.1038/s41467-025-56402-y |
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