Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria.
Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria.
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DOI：
10.1371/journal.pone.0016060
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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：
Kitamura N;Nakamura Y;Miyamoto Y;Miyamoto T;Kabu K;Yoshida M;Futamura M;Ichinose S;Arakawa H
保持健康的线粒体可以防止衰老、癌症和各种退行性疾病，这些疾病是由于线粒体质量控制(MQC)缺陷造成的。最近，我们发现了MQC的一种新机制，即MIEAP诱导线粒体内溶酶体样细胞器，在清除氧化的线粒体蛋白中起关键作用(MIEAP诱导线粒体内溶酶体样细胞器积聚的MALM)。然而，MQC的很大一部分机制仍不清楚。在这里，我们报告了MIEAP调节的MQC的额外机制。活性氧(ROS)清除剂能完全抑制MALM。线粒体外膜蛋白Nix通过Nix的BH3结构域和Mieap的盘绕线圈结构域与Mieap以ROS依赖的方式相互作用。Nix的缺乏也完全损害了MALM。当MALM被抑制时，MIEAP诱导了类空泡样结构(MIV，MIEAP诱导的空泡)，这些结构通过积累溶酶体吞噬和降解不健康的线粒体。P53的失活严重损害了MALM和MIV的生成，导致不健康的线粒体积累。这些结果表明：(1)线粒体ROS和NIX是MALM的必需因子；(2)MIV是线粒体溶酶体降解的新机制；(3)P53-Mieap通路分别通过MALM和MIV的产生修复或消除不健康的线粒体，在MQC中发挥关键作用。
Maintenance of healthy mitochondria prevents aging, cancer, and a variety of degenerative diseases that are due to the result of defective mitochondrial quality control (MQC). Recently, we discovered a novel mechanism for MQC, in which Mieap induces intramitochondrial lysosome-like organella that plays a critical role in the elimination of oxidized mitochondrial proteins (designated MALM for Mieap-induced accumulation of lysosome-like organelles within mitochondria). However, a large part of the mechanisms for MQC remains unknown. Here, we report additional mechanisms for Mieap-regulated MQC. Reactive oxygen species (ROS) scavengers completely inhibited MALM. A mitochondrial outer membrane protein NIX interacted with Mieap in a ROS-dependent manner via the BH3 domain of NIX and the coiled-coil domain of Mieap. Deficiency of NIX also completely impaired MALM. When MALM was inhibited, Mieap induced vacuole-like structures (designated as MIV for Mieap-induced vacuole), which engulfed and degraded the unhealthy mitochondria by accumulating lysosomes. The inactivation of p53 severely impaired both MALM and MIV generation, leading to accumulation of unhealthy mitochondria. These results suggest that (1) mitochondrial ROS and NIX are essential factors for MALM, (2) MIV is a novel mechanism for lysosomal degradation of mitochondria, and (3) the p53-Mieap pathway plays a pivotal role in MQC by repairing or eliminating unhealthy mitochondria via MALM or MIV generation, respectively.
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影响因子：
4.7
作者：
Friguet, Bertrand;Bulteau, Anne-Laure;Petropoulos, Isabelle
通讯作者：
Petropoulos, Isabelle
影响因子：
56.9
作者：
Ishikawa, Kaori;Takenaga, Keizo;Hayashi, Jun-Ichi
通讯作者：
Hayashi, Jun-Ichi
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。
影响因子：
3.7
作者：
Miyamoto Y;Kitamura N;Nakamura Y;Futamura M;Miyamoto T;Yoshida M;Ono M;Ichinose S;Arakawa H
通讯作者：
Arakawa H
ATG32是一种线粒体蛋白，在线粒体过程中赋予了选择性。
影响因子：
11.8
作者：
Kanki, Tomotake;Wang, Ke;Cao, Yang;Baba, Misuzu;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.
DOI：
10.1083/jcb.200809125
发表时间：
2008-12-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Narendra D;Tanaka A;Suen DF;Youle RJ
通讯作者：
Youle RJ