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SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters

Author

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  • Mingyang Chen

    (Zhejiang University
    Jinhua Institute of Zhejiang University)

  • Luexiang Yuan

    (Zhejiang University)

  • Binxin Chen

    (Zhejiang University
    Westlake University)

  • Hui Chang

    (Zhejiang University)

  • Jun Luo

    (Zhejiang University
    Westlake University)

  • Hengbin Zhang

    (Zhejiang University)

  • Zhongjian Chen

    (Chinese Academy of Sciences)

  • Jiao Kong

    (Zhejiang University)

  • Yaodong Yi

    (Zhejiang University)

  • Mengru Bai

    (Westlake University)

  • Minlei Dong

    (Zhejiang University)

  • Hui Zhou

    (Zhejiang University
    Jinhua Institute of Zhejiang University)

  • Huidi Jiang

    (Zhejiang University
    Jinhua Institute of Zhejiang University)

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.

Suggested Citation

  • 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, 2025. "SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56402-y
    DOI: 10.1038/s41467-025-56402-y
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