• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

烟酰胺腺嘌呤二核苷酸被转运进入哺乳动物线粒体。

Nicotinamide adenine dinucleotide is transported into mammalian mitochondria.

机构信息

Department of Physiology, Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

PARC, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States.

出版信息

Elife. 2018 Jun 12;7:e33246. doi: 10.7554/eLife.33246.

DOI:10.7554/eLife.33246
PMID:29893687
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6013257/
Abstract

Mitochondrial NAD levels influence fuel selection, circadian rhythms, and cell survival under stress. It has alternately been argued that NAD in mammalian mitochondria arises from import of cytosolic nicotinamide (NAM), nicotinamide mononucleotide (NMN), or NAD itself. We provide evidence that murine and human mitochondria take up intact NAD. Isolated mitochondria preparations cannot make NAD from NAM, and while NAD is synthesized from NMN, it does not localize to the mitochondrial matrix or effectively support oxidative phosphorylation. Treating cells with nicotinamide riboside that is isotopically labeled on the nicotinamide and ribose moieties results in the appearance of doubly labeled NAD within mitochondria. Analogous experiments with doubly labeled nicotinic acid riboside (labeling cytosolic NAD without labeling NMN) demonstrate that NAD(H) is the imported species. Our results challenge the long-held view that the mitochondrial inner membrane is impermeable to pyridine nucleotides and suggest the existence of an unrecognized mammalian NAD (or NADH) transporter.

摘要

线粒体 NAD 水平影响燃料选择、昼夜节律和应激下的细胞存活。人们一直认为哺乳动物线粒体中的 NAD 来源于细胞质中的烟酰胺 (NAM)、烟酰胺单核苷酸 (NMN) 或 NAD 的导入。我们提供的证据表明，鼠和人线粒体摄取完整的 NAD。分离的线粒体制剂不能从 NAM 制造 NAD，尽管 NAD 可以从 NMN 合成，但它不会定位于线粒体基质或有效地支持氧化磷酸化。用在烟酰胺和核糖部分被同位素标记的烟酰胺核苷处理细胞，导致线粒体中出现双标记的 NAD。用双标记的烟酸核苷（标记细胞质 NAD 而不标记 NMN）进行类似的实验表明，NAD(H) 是被导入的物质。我们的结果挑战了线粒体内膜对吡啶核苷酸不可渗透的长期观点，并表明存在一种未被识别的哺乳动物 NAD（或 NADH）转运蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/9417d4b5c8cd/elife-33246-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/af71851c84e0/elife-33246-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/141064a5997e/elife-33246-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/c206d8acbb1f/elife-33246-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/67346281ffd1/elife-33246-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/684b0a1707cb/elife-33246-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/5899a9071ee7/elife-33246-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/ce3d9377318a/elife-33246-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/1575d4c7c9c0/elife-33246-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/6d0f27b48fad/elife-33246-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/38c24b044b37/elife-33246-fig6-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/9417d4b5c8cd/elife-33246-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/af71851c84e0/elife-33246-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/141064a5997e/elife-33246-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/c206d8acbb1f/elife-33246-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/67346281ffd1/elife-33246-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/684b0a1707cb/elife-33246-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/5899a9071ee7/elife-33246-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/ce3d9377318a/elife-33246-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/1575d4c7c9c0/elife-33246-fig6-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/6d0f27b48fad/elife-33246-fig6-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/38c24b044b37/elife-33246-fig6-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7e/6013257/9417d4b5c8cd/elife-33246-fig7.jpg

相似文献

1
Nicotinamide adenine dinucleotide is transported into mammalian mitochondria.烟酰胺腺嘌呤二核苷酸被转运进入哺乳动物线粒体。
Elife. 2018 Jun 12;7:e33246. doi: 10.7554/eLife.33246.
2
Reversal of endothelial dysfunction by nicotinamide mononucleotide via extracellular conversion to nicotinamide riboside.烟酰胺单核苷酸通过细胞外转化为烟酰胺核糖核苷来逆转内皮功能障碍。
Biochem Pharmacol. 2020 Aug;178:114019. doi: 10.1016/j.bcp.2020.114019. Epub 2020 May 8.
3
Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells.烟酰胺核糖激酶在介导骨骼肌细胞中的烟酰胺单核苷酸和烟酰胺核糖代谢中表现出冗余性。
Mol Metab. 2017 May 29;6(8):819-832. doi: 10.1016/j.molmet.2017.05.011. eCollection 2017 Aug.
4
Rat liver mitochondria can synthesize nicotinamide adenine dinucleotide from nicotinamide mononucleotide and ATP via a putative matrix nicotinamide mononucleotide adenylyltransferase.大鼠肝脏线粒体可通过一种假定的基质烟酰胺单核苷酸腺苷酰转移酶，由烟酰胺单核苷酸和ATP合成烟酰胺腺嘌呤二核苷酸。
Biochem Mol Biol Int. 1996 Feb;38(2):297-306.
5
Equilibrative Nucleoside Transporters Mediate the Import of Nicotinamide Riboside and Nicotinic Acid Riboside into Human Cells.平衡型核苷转运体介导烟酰胺核糖和烟酸核糖进入人类细胞。
Int J Mol Sci. 2021 Jan 30;22(3):1391. doi: 10.3390/ijms22031391.
6
NAD Intermediates: The Biology and Therapeutic Potential of NMN and NR.NAD 中间体：NMN 和 NR 的生物学和治疗潜力。
Cell Metab. 2018 Mar 6;27(3):513-528. doi: 10.1016/j.cmet.2017.11.002. Epub 2017 Dec 14.
7
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.NRK1 调控哺乳动物细胞中烟酰胺单核苷酸和烟酰胺核苷的代谢。
Nat Commun. 2016 Oct 11;7:13103. doi: 10.1038/ncomms13103.
8
NadN and e (P4) are essential for utilization of NAD and nicotinamide mononucleotide but not nicotinamide riboside in Haemophilus influenzae.NadN和e（P4）对于流感嗜血杆菌利用烟酰胺腺嘌呤二核苷酸（NAD）和烟酰胺单核苷酸至关重要，但对于利用烟酰胺核糖并非如此。
J Bacteriol. 2001 Jul;183(13):3974-81. doi: 10.1128/JB.183.13.3974-3981.2001.
9
Nucleoside salvage pathway for NAD biosynthesis in Salmonella typhimurium.鼠伤寒沙门氏菌中烟酰胺腺嘌呤二核苷酸（NAD）生物合成的核苷补救途径。
J Bacteriol. 1982 Dec;152(3):1111-6. doi: 10.1128/jb.152.3.1111-1116.1982.
10
Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism.通过烟酰胺磷酸核糖转移酶增加肌肉中的NAD合成不足以促进氧化代谢。
J Biol Chem. 2015 Jan 16;290(3):1546-58. doi: 10.1074/jbc.M114.579565. Epub 2014 Nov 19.

引用本文的文献

1
13C tracing in synaptosomes reveals that SGLT2 inhibition with dapagliflozin prevents metabolic deficits in the 5X-FAD model of Alzheimer's Disease.在突触体中进行的13C追踪显示，用达格列净抑制SGLT2可预防阿尔茨海默病5X-FAD模型中的代谢缺陷。
bioRxiv. 2025 May 3:2025.04.30.651373. doi: 10.1101/2025.04.30.651373.
2
Neuroprotection by Mitochondrial NAD Against Glutamate-Induced Excitotoxicity.线粒体烟酰胺腺嘌呤二核苷酸对谷氨酸诱导的兴奋性毒性的神经保护作用。
Cells. 2025 Apr 12;14(8):582. doi: 10.3390/cells14080582.
3
Mitochondrial NAD deficiency in vascular smooth muscle impairs collagen III turnover to trigger thoracic and abdominal aortic aneurysm.

本文引用的文献

1
Mouse Nudt13 is a Mitochondrial Nudix Hydrolase with NAD(P)H Pyrophosphohydrolase Activity.小鼠Nudt13是一种具有NAD(P)H焦磷酸水解酶活性的线粒体Nudix水解酶。
Protein J. 2017 Oct;36(5):425-432. doi: 10.1007/s10930-017-9734-x.
2
Metabolite Spectral Accuracy on Orbitraps.轨道阱代谢物谱精度。
Anal Chem. 2017 Jun 6;89(11):5940-5948. doi: 10.1021/acs.analchem.7b00396. Epub 2017 May 18.
3
Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics.线粒体 NUDIX 水解酶：NAD 分解代谢、GTP 和线粒体动态之间的代谢联系。
血管平滑肌中的线粒体烟酰胺腺嘌呤二核苷酸缺乏会损害Ⅲ型胶原蛋白的更新，从而引发胸主动脉瘤和腹主动脉瘤。
Nat Cardiovasc Res. 2025 Mar;4(3):275-292. doi: 10.1038/s44161-024-00606-w. Epub 2025 Jan 22.
4
Subcellular NAD pools are interconnected and buffered by mitochondrial NAD.亚细胞NAD池相互连接，并由线粒体NAD缓冲。
Nat Metab. 2024 Dec;6(12):2319-2337. doi: 10.1038/s42255-024-01174-w. Epub 2024 Dec 13.
5
NAD metabolism and heart failure: Mechanisms and therapeutic potentials.NAD 代谢与心力衰竭：机制与治疗潜能。
J Mol Cell Cardiol. 2024 Oct;195:45-54. doi: 10.1016/j.yjmcc.2024.07.008. Epub 2024 Aug 3.
6
Regulation of and challenges in targeting NAD metabolism.靶向 NAD 代谢的调控及挑战。
Nat Rev Mol Cell Biol. 2024 Oct;25(10):822-840. doi: 10.1038/s41580-024-00752-w. Epub 2024 Jul 18.
7
Novel insight into nicotinamide adenine dinucleotide and related metabolites in cancer patients undergoing surgery.对接受手术的癌症患者体内烟酰胺腺嘌呤二核苷酸及相关代谢物的新见解。
Sci Rep. 2024 Jul 17;14(1):16557. doi: 10.1038/s41598-024-66004-1.
8
The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity.TAS1R2 G 蛋白偶联受体是骨骼肌中的环境葡萄糖传感器，可调节 NAD 动态平衡和线粒体容量。
Nat Commun. 2024 Jun 8;15(1):4915. doi: 10.1038/s41467-024-49100-8.
9
Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure.抑制 HSD17B8 可抑制由 PTEN 失活引起的细胞增殖。
Sci Rep. 2024 May 29;14(1):12280. doi: 10.1038/s41598-024-63052-5.
10
Mitochondrial dysfunction in long COVID: mechanisms, consequences, and potential therapeutic approaches.长新冠中的线粒体功能障碍：机制、后果和潜在治疗方法。
Geroscience. 2024 Oct;46(5):5267-5286. doi: 10.1007/s11357-024-01165-5. Epub 2024 Apr 26.
Neurochem Int. 2017 Oct;109:193-201. doi: 10.1016/j.neuint.2017.03.009. Epub 2017 Mar 14.
4
NRK1 controls nicotinamide mononucleotide and nicotinamide riboside metabolism in mammalian cells.NRK1 调控哺乳动物细胞中烟酰胺单核苷酸和烟酰胺核苷的代谢。
Nat Commun. 2016 Oct 11;7:13103. doi: 10.1038/ncomms13103.
5
Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle.NAD 稳态失衡导致骨骼肌进行性和可逆性退变。
Cell Metab. 2016 Aug 9;24(2):269-82. doi: 10.1016/j.cmet.2016.07.005.
6
Biosensor reveals multiple sources for mitochondrial NAD⁺.生物传感器揭示了线粒体 NAD⁺的多种来源。
Science. 2016 Jun 17;352(6292):1474-7. doi: 10.1126/science.aad5168.
7
Nmnat3 Is Dispensable in Mitochondrial NAD Level Maintenance In Vivo.Nmnat3在体内线粒体NAD水平维持中并非必需。
PLoS One. 2016 Jan 12;11(1):e0147037. doi: 10.1371/journal.pone.0147037. eCollection 2016.
8
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins.线粒体蛋白质组数据库2.0：哺乳动物线粒体蛋白的更新清单。
Nucleic Acids Res. 2016 Jan 4;44(D1):D1251-7. doi: 10.1093/nar/gkv1003. Epub 2015 Oct 7.
9
Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells.胞质溶胶与线粒体之间NAD⁺的亚细胞分布决定人类细胞的代谢特征。
J Biol Chem. 2015 Nov 13;290(46):27644-59. doi: 10.1074/jbc.M115.654129. Epub 2015 Oct 2.
10
The human SLC25A33 and SLC25A36 genes of solute carrier family 25 encode two mitochondrial pyrimidine nucleotide transporters.溶质载体家族25的人类SLC25A33和SLC25A36基因编码两种线粒体嘧啶核苷酸转运蛋白。
J Biol Chem. 2014 Nov 28;289(48):33137-48. doi: 10.1074/jbc.M114.610808. Epub 2014 Oct 15.