Mitochondrial dysfunction leads to telomere attrition and genomic instability
Mitochondrial dysfunction leads to telomere attrition and genomic instability
复制标题
DOI：
10.1046/j.1474-9728.2002.00004.x
复制
发表时间：
2002-10-01
期刊：
影响因子：
7.8
通讯作者：
Keefe, DL
中科院分区：
文献类型：
--
作者：
Liu, L;Trimarchi, JR;Keefe, DL
线粒体功能障碍和氧化应激与细胞衰老、细胞凋亡、衰老和衰老相关的病理学有关。端粒缩短和基因组不稳定性也与复制性衰老、衰老和癌症有关。在这里，我们表明，线粒体功能障碍导致端粒磨损，端粒丢失，染色体融合和断裂，伴随着细胞凋亡。一种抗氧化剂可以防止线粒体功能障碍细胞中的端粒丢失和基因组不稳定性，这表明活性氧是连接线粒体功能障碍和基因组不稳定性的介质。此外，核移植保护基因组免受端粒功能障碍，并通过与功能性线粒体的重建促进细胞存活。这项工作将线粒体功能障碍和基因组不稳定性联系起来，并可能提供新的治疗策略来对抗某些线粒体和衰老相关的病理。
Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging-associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging-associated pathologies.