SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters

  • Nat Commun. 2025 Jan 30;16(1):1181. doi: 10.1038/s41467-025-56402-y.
Mingyang Chen  #  1  2 ,  Luexiang Yuan  #  1 ,  Binxin Chen  1  3 ,  Hui Chang  4 ,  Jun Luo  1  3 ,  Hengbin Zhang  1 ,  Zhongjian Chen  5 ,  Jiao Kong  1 ,  Yaodong Yi  1 ,  Mengru Bai  3 ,  Minlei Dong  1 ,  Hui Zhou  6  7 ,  Huidi Jiang  8  9
Affiliations
  • 1. College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China.
  • 2. Jinhua Institute of Zhejiang University, Jinhua, China.
  • 3. Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Westlake University, Hangzhou, China.
  • 4. Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders, Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou, China.
  • 5. Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, China.
  • 6. College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China. [email protected].
  • 7. Jinhua Institute of Zhejiang University, Jinhua, China. [email protected].
  • 8. College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China. [email protected].
  • 9. Jinhua Institute of Zhejiang University, Jinhua, China. [email protected].
  • # Contributed equally.
PMID: 39885119 DOI: 10.1038/s41467-025-56402-y
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.