|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ИНХС РАН |
||
Pathways and subcellular compartmentation of NAD biosynthesis in human cells: From entry of extracellular precursors to mitochondrial NAD generationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 1 апреля 2017 г.
- Авторы: Nikiforov A., Dölle C., Niere M., Ziegler M.
- Журнал: Journal of Biological Chemistry
- Том: 286
- Номер: 24
- Год издания: 2011
- Издательство: American Society for Biochemistry and Molecular Biology Inc.
- Местоположение издательства: United States
- Первая страница: 21767
- Последняя страница: 21778
- DOI: 10.1074/jbc.M110.213298
- Аннотация: NAD is a vital redox carrier, and its degradation is a key element of important regulatory pathways. NAD-mediated functions are compartmentalized and have to be fueled by specific biosynthetic routes. However, little is known about the different pathways, their subcellular distribution, and regulation in human cells. In particular, the route(s) to generate mitochondrial NAD, the largest subcellular pool, is still unknown. To visualize organellar NAD changes in cells, we targeted poly-(ADP-ribose) polymerase activity into the mitochondrial matrix. This activity synthesized immunodetectable poly(ADP-ribose) depending on mitochondrial NAD availability. Based on this novel detector system, detailed subcellular enzyme localizations, and pharmacological inhibitors, we identified extracellular NAD precursors, their cytosolic conversions, and the pathway of mitochondrial NAD generation. Our results demonstrate that, besides nicotinamide and nicotinic acid, only the corresponding nucleosides readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors. These precursors can all be converted to cytosolic and mitochondrial NAD. For mitochondrial NAD synthesis, precursors are converted to NMN in the cytosol. When taken up into the organelles, NMN (together with ATP) serves as substrate of NMNAT3 to form NAD. NMNAT3 was conclusively localized to the mitochondrial matrix and is the only known enzyme of NAD synthesis residing within these organelles. We thus present a comprehensive dissection of mammalian NAD biosynthesis, the groundwork to understand regulation of NAD-mediated processes, and the organismal homeostasis of this fundamental molecule. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
- Добавил в систему: Никифоров Андрей Анатольевич