Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress
Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress
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DOI：
10.1242/jcs.019372
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发表时间：
2008-04-01
影响因子：
4
通讯作者：
Saretzki, Gabriele
中科院分区：
文献类型：
--
作者：
Ahmed, Shaheda;Passos, Joao F.;Saretzki, Gabriele
端粒酶是一种核糖核蛋白，可以抵消端粒缩短，并可以使人类细胞永生。也有证据表明端粒酶的端粒非依赖性生存功能。然而，其机制尚不清楚。我们在这里表明，端粒酶催化亚基，保护人类成纤维细胞免受氧化应激。虽然在标准条件下，端粒酶维持端粒长度，但在增加的压力下，端粒缩短的速度与没有活性端粒酶的细胞一样快。这是因为在应激下，TERT以剂量和时间依赖性方式可逆地从细胞核中排除。核外端粒酶与线粒体共定位。在TERT过表达的细胞中，线粒体DNA受到保护，线粒体膜电位增加，线粒体超氧化物产生和细胞过氧化物水平降低，所有这些都表明线粒体功能改善和逆行反应减弱。我们建议保护线粒体在温和的压力作为一个新的功能的端粒酶。
Telomerase is a ribonucleoprotein that counteracts telomere shortening and can immortalise human cells. There is also evidence for a telomere-independent survival function of telomerase. However, its mechanism is not understood. We show here that TERT, the catalytic subunit of human telomerase, protects human fibroblasts against oxidative stress. While TERT maintains telomere length under standard conditions, telomeres under increased stress shorten as fast as in cells without active telomerase. This is because TERT is reversibly excluded from the nucleus under stress in a dose- and time-dependent manner. Extranuclear telomerase colocalises with mitochondria. In TERT-overexpressing cells, mtDNA is protected, mitochondrial membrane potential is increased and mitochondrial superoxide production and cell peroxide levels are decreased, all indicating improved mitochondrial function and diminished retrograde response. We propose protection of mitochondria under mild stress as a novel function of TERT.