Mitochondrial quality control during inheritance is associated with lifespan and mother-daughter age asymmetry in budding yeast.
Mitochondrial quality control during inheritance is associated with lifespan and mother-daughter age asymmetry in budding yeast.
复制标题
DOI：
10.1111/j.1474-9726.2011.00731.x
复制
发表时间：
2011-10
期刊：
影响因子：
7.8
通讯作者：
Pon LA
中科院分区：
文献类型：
--
作者：
McFaline-Figueroa JR;Vevea J;Swayne TC;Zhou C;Liu C;Leung G;Boldogh IR;Pon LA
光漂白实验中的荧光损失以及使用超氧化物和氧化还原电位生物传感器对线粒体功能的分析表明，单个酵母细胞中的线粒体在物理和功能上是不同的。在酵母细胞分裂过程中保留在母细胞中的线粒体与芽中的线粒体相比，具有显著较低的氧化还原电位和较高的超氧化物水平。氧化还原电位较低的线粒体在母细胞中的保留程度与年轻和老年细胞中相同，这可以解释酵母从0-5代老化时细胞总线粒体氧化还原潜力随年龄的下降。Mmr1p是DSL1系留蛋白家族的成员，定位于芽尖的线粒体，是正常线粒体遗传所必需的。Mmr1p的缺失会导致线粒体质量控制和复制寿命(RLS)的异质性。与野生型细胞相比，长期存活的mmr1Δ细胞表现出延长的RLS，减少的平均世代时间，增加的线粒体氧化还原电位和较低的线粒体超氧化物水平。短命的MMR1Δ细胞表现出相反的表型。此外，短寿命的细胞只产生短寿命的细胞，而长寿命细胞的大多数子代细胞是长寿命的。这些发现支持这样的模型，即线粒体遗传机制促进母细胞中功能较低的线粒体的保留，这一过程导致母女年龄不对称和与年龄相关的细胞适合性下降。
Fluorescence loss in photobleaching experiments and analysis of mitochondrial function using superoxide and redox potential biosensors revealed that mitochondria within individual yeast cells are physically and functionally distinct. Mitochondria that are retained in mother cells during yeast cell division have significantly lower redox potential and higher superoxide levels compared to mitochondria in buds. Retention of mitochondria with lower redox potential in mother cells occurs to the same extent in young and older cells, and can account for the age-associated decline in total cellular mitochondrial redox potential in yeast as they age from 0–5 generations. Deletion of Mmr1p, a member of the DSL1 family of tethering proteins that localizes to mitochondria at the bud tip and is required for normal mitochondrial inheritance, produces defects in mitochondrial quality control and heterogeneity in replicative lifespan (RLS). Long-lived mmr1Δ cells exhibit prolonged RLS, reduced mean generation times, increased mitochondrial redox potential and lower mitochondrial superoxide levels compared to wild-type cells. Short-lived mmr1Δ cells exhibit the opposite phenotypes. Moreover, short-lived cells give rise exclusively to short-lived cells, while the majority of daughters of long-lived cells are long lived. These findings support the model that the mitochondrial inheritance machinery promotes retention of lower-functioning mitochondria in mother cells and that this process contributes to both mother-daughter age asymmetry and age-associated declines in cellular fitness.
登录
查看更多内容
DOI：
10.1016/j.cub.2009.08.041
发表时间：
2009-11-03
期刊：
Current biology : CB
影响因子：
--
作者：
García-Rodríguez LJ;Crider DG;Gay AC;Salanueva IJ;Boldogh IR;Pon LA
通讯作者：
Pon LA
影响因子：
10.5
作者：
Lin, SJ;Ford, E;Guarente, L
通讯作者：
Guarente, L
DOI：
10.1073/pnas.0804550105
发表时间：
2008-12-02
影响因子：
11.1
作者：
Erjavec, N.;Cvijovic, M.;Nystrom, T.
通讯作者：
Nystrom, T.
影响因子：
11.4
作者：
Collins, TJ;Berridge, MJ;Bootman, MD
通讯作者：
Bootman, MD
影响因子：
7.4
作者：
Harris, N;Costa, V;Piper, PW
通讯作者：
Piper, PW