作者
Ana P Gomes, Nathan L Price, Alvin JY Ling, Javid J Moslehi, Magdalene K Montgomery, Luis Rajman, James P White, João S Teodoro, Christiane D Wrann, Basil P Hubbard, Evi M Mercken, Carlos M Palmeira, Rafael De Cabo, Anabela P Rolo, Nigel Turner, Eric L Bell, David A Sinclair
发表日期
2013/12/19
期刊
Cell
卷号
155
期号
7
页码范围
1624-1638
出版商
Elsevier
简介
Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD+ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD+ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β …
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AP Gomes, NL Price, AJY Ling, JJ Moslehi… - Cell, 2013