Mitochondrial protein quality control: Implications in ageing
Mitochondrial protein quality control: Implications in ageing
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DOI：
10.1002/biot.200800041
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
Petropoulos, Isabelle
中科院分区：
文献类型：
--
作者：
Friguet, Bertrand;Bulteau, Anne-Laure;Petropoulos, Isabelle
线粒体既是活性氧 (ROS) 产生的主要来源，也是氧化大分子损伤的靶标。 ROS 产生的增加和氧化蛋白质的积累与细胞衰老有关。蛋白质质量控制，也称为蛋白质维护，对于通过降解和修复消除氧化蛋白质非常重要。伴侣蛋白与错误折叠蛋白的重折叠有关，而氧化蛋白修复仅限于特定酶系统催化还原含硫氨基酸、半胱氨酸和甲硫氨酸的某些氧化产物。在线粒体中，蛋白质内蛋氨酸残基的氧化可以通过蛋氨酸亚砜还原酶催化逆转，蛋氨酸亚砜还原酶是一种普遍存在的酶系统，与衰老和抗氧化应激有关。不可逆氧化的蛋白质会被线粒体基质蛋白水解系统（例如 Lon 蛋白酶）降解。 ATP 刺激的 Lon 蛋白酶被认为在线粒体内氧化蛋白的降解中发挥着至关重要的作用，并且先前已报道过该蛋白水解系统的活性和/或表达与年龄相关的下降。因此，与年龄相关的线粒体蛋白质维持受损可能会导致与年龄相关的氧化蛋白质的积累和线粒体氧化还原稳态的受损。
Mitochondria represent both a major source for reactive oxygen species (ROS) production and a target for oxidative macromolecular damage. increased production of ROS and accumulation of oxidized proteins have been associated with cellular ageing. Protein quality control, also referred as protein maintenance, is very important for the elimination of oxidized proteins through degradation and repair. Chaperone proteins have been implicated in refolding of misfolded proteins while oxidized protein repair is limited to the catalyzed reduction of certain oxidation products of the sulfur-containing amino acids, cysteine and methionine, by specific enzymatic systems. In the mitochondria, oxidation of methionine residues within proteins can be catalytically reversed by the methionine sulfoxide reductases, an ubiquitous enzymatic system that has been implicated both in ageing and protection against oxidative stress. Irreversibly oxidized proteins are targeted to degradation by mitochondrial matrix proteolytic systems such as the Lon protease. The ATP-stimulated Lon protease is believed to play a crucial role in the degradation of oxidized proteins within the mitochondria and age-related declines in the activity and/or expression of this proteolytic system have been previously reported. Age-related impairment of mitochondrial protein maintenance may therefore contribute to the age-associated build-up of oxidized proteins and impairment of mitochondrial redox homeostasis.