近日，天津医科大学王婷团队的最新研究揭示了SelO催化的NAD+水解是线粒体稳态所必需的。这一研究成果发表在2026年3月9日出版的国际学术期刊《细胞》上。
通过对潜在的NAD结合蛋白的硅筛选，研究人员发现了一个线粒体反应，在这个反应中，NAD+被SELENOO （SelO）水解成烟酰胺单核苷酸（NMN）和AMP，以Mn2+为辅助因子。催化作用依赖于SelO的硒代半胱氨酸-丝氨酸-丝氨酸（CSS）C端残基，特别是硒代半胱氨酸667。除了广泛的代谢作用外，该反应还通过与脂肪酸氧化（FAO）酶直接相关的SelO在脂质利用中起着显著作用，并且在哺乳动物细胞和细菌中都是保守的。这种反应是对基质pH值升高的响应，这是线粒体呼吸增强的信号，并保护线粒体免受持续代谢过度激活。这些发现揭示了NAD+时空调控的保守机制，并强调了其在原核生物和真核生物中的生理意义。
据介绍，烟酰胺腺嘌呤二核苷酸（NAD+）的调控在许多生命过程中起着至关重要的作用。然而，导致线粒体中NAD+降解的机制仍然不够明确。
附：英文原文
Title: NAD+ hydrolysis catalyzed by SelO is required for mitochondrial homeostasis
Author: Xiaofan Jia, Teng Zhang, Chenxi Yang, Kaiyang Liu, Li Wu, Longfei Diao, Yuting Yang, Jie Wu, Yeyi Li, Weiyan Sun, Kai Zhang, Yuhui Jiang, Yuzheng Zhao, Xu Zhang, Peng Jiang, Yideng Jiang, Qiujing Yu, Song Xiang, Yuan Fu, Ting Wang
Issue&Volume: 2026-03-09
Abstract: The regulation of nicotinamide adenine dinucleotide (NAD+) is crucial for numerous life processes. However, the mechanisms leading to NAD+ degradation in mitochondria remain insufficiently defined. Through in silico screening of potential NAD-binding proteins, we discovered a mitochondrial reaction in which NAD+ is hydrolyzed to nicotinamide mononucleotide (NMN) and AMP by SELENOO (SelO), using Mn2+ as cofactor. Catalysis depends on SelO’s selenocysteine-serine-serine (CSS) C-terminal residues, particularly the selenocysteine 667. In addition to broad metabolic effects, this reaction plays a pronounced role in lipid utilization via SelO directly associating with fatty acid oxidation (FAO) enzymes, and it is conserved in both mammalian cells and bacteria. This reaction is responsive to elevated matrix pH, a signal of enhanced mitochondrial respiration, and protects mitochondria from sustained metabolic overactivation. These findings reveal a conserved mechanism for spatiotemporal NAD+ regulation and highlight its physiological significance in both prokaryotes and eukaryotes.
DOI: 10.1016/j.cell.2026.01.033
Source: https://www.cell.com/cell/abstract/S0092-8674(26)00161-3