Possible existence of lysosome-like organella within mitochondria and its role in mitochondrial quality control.
Possible existence of lysosome-like organella within mitochondria and its role in mitochondrial quality control.
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线粒体内可能存在溶酶体样细胞器及其在线粒体质量控制中的作用。
DOI：
10.1371/journal.pone.0016054
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发表时间：
2011-01-17
期刊：
影响因子：
3.7
通讯作者：
Arakawa H
中科院分区：
文献类型：
--
作者：
Miyamoto Y;Kitamura N;Nakamura Y;Futamura M;Miyamoto T;Yoshida M;Ono M;Ichinose S;Arakawa H
不健康线粒体的积累导致线粒体功能障碍，这与衰老、癌症和各种退行性疾病有关。然而，线粒体质量调节的机制仍不清楚。在这里，我们表明，Mieap，一种新的p53诱导蛋白，诱导线粒体内溶酶体样细胞器，在线粒体质量控制中起着至关重要的作用。Mieap表达受p53直接调节，并且由于DNA甲基化而经常在人类癌症中丢失。Mieap显著诱导溶酶体蛋白在线粒体内的积累和线粒体酸性条件，而不破坏线粒体结构（命名为MALM，用于Mieap诱导的溶酶体样细胞器在线粒体内的积累），以响应线粒体损伤。MALM与典型的自噬无关。MALM参与氧化线粒体蛋白的降解，导致ATP合成增加和活性氧产生减少。这些结果表明，Mieap诱导线粒体内溶酶体样细胞器，通过消除氧化的线粒体蛋白质在线粒体质量控制中起着关键作用。由于p53突变和/或Mieap甲基化，癌细胞可能积累不健康的线粒体，这是瓦尔堡效应的潜在原因。
The accumulation of unhealthy mitochondria results in mitochondrial dysfunction, which has been implicated in aging, cancer, and a variety of degenerative diseases. However, the mechanism by which mitochondrial quality is regulated remains unclear. Here, we show that Mieap, a novel p53-inducible protein, induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control. Mieap expression is directly regulated by p53 and is frequently lost in human cancer as result of DNA methylation. Mieap dramatically induces the accumulation of lysosomal proteins within mitochondria and mitochondrial acidic condition without destroying the mitochondrial structure (designated MALM, for Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage. MALM was not related to canonical autophagy. MALM is involved in the degradation of oxidized mitochondrial proteins, leading to increased ATP synthesis and decreased reactive oxygen species generation. These results suggest that Mieap induces intramitochondrial lysosome-like organella that plays a critical role in mitochondrial quality control by eliminating oxidized mitochondrial proteins. Cancer cells might accumulate unhealthy mitochondria due to p53 mutations and/or Mieap methylation, representing a potential cause of the Warburg effect.
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影响因子：
30.8
作者：
Bourdon, Alice;Minai, Limor;Rotig, Agnes
通讯作者：
Rotig, Agnes
影响因子：
4.7
作者：
Friguet, Bertrand;Bulteau, Anne-Laure;Petropoulos, Isabelle
通讯作者：
Petropoulos, Isabelle
DOI：
10.1007/bf01233159
发表时间：
1992-03-01
期刊：
SOMATIC CELL AND MOLECULAR GENETICS
影响因子：
--
作者：
HAYASHI, JI;TAKEMITSU, M;NONAKA, I
通讯作者：
NONAKA, I
DOI：
10.1083/jcb.200708199
发表时间：
2007-11-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kutik S;Guiard B;Meyer HE;Wiedemann N;Pfanner N
通讯作者：
Pfanner N
影响因子：
5
作者：
Baines, Christopher P.
通讯作者：
Baines, Christopher P.