Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space.
Small heat shock proteins operate as molecular chaperones in the mitochondrial intermembrane space.
复制标题
DOI：
10.1038/s41556-022-01074-9
复制
发表时间：
2023-03
影响因子：
21.3
通讯作者：
Timmerman, Vincent
中科院分区：
文献类型：
--
作者：
Adriaenssens, Elias;Asselbergh, Bob;Rivera-Mejias, Pablo;Bervoets, Sven;Vendredy, Leen;De Winter, Vicky;Spaas, Katrien;de Rycke, Riet;van Isterdael, Gert;Impens, Francis;Langer, Thomas;Timmerman, Vincent
线粒体是具有不同隔室的复杂细胞器，每个隔室都有自己的蛋白质质量控制因子。虽然线粒体基质的分子伴侣被很好地表征，但对哪些分子伴侣保护线粒体膜间隙知之甚少。在这里，我们表明，胞质小热休克蛋白进口到线粒体膜间隙的基础条件下，在那里他们作为分子伴侣。线粒体膜间隙中的蛋白质错误折叠导致小的热休克蛋白的募集增加。小的热休克蛋白的消耗导致线粒体肿胀和呼吸减少，而聚集的聚集倾向的基板在他们的存在被反击。Charcot-Marie-Tooth疾病引起的突变干扰了HSPB 1的线粒体功能，可能将先前观察到的Charcot-Marie-Tooth 2F型线粒体功能障碍与其在线粒体膜间隙中的作用联系起来。我们的研究结果表明，小的热休克蛋白形成了一个伴侣系统，在线粒体膜间隙。Adriaenssens等人提供的证据表明，细胞溶质小热休克蛋白定位于线粒体膜间隙，在那里它们作为分子伴侣发挥作用。
Mitochondria are complex organelles with different compartments, each harbouring their own protein quality control factors. While chaperones of the mitochondrial matrix are well characterized, it is poorly understood which chaperones protect the mitochondrial intermembrane space. Here we show that cytosolic small heat shock proteins are imported under basal conditions into the mitochondrial intermembrane space, where they operate as molecular chaperones. Protein misfolding in the mitochondrial intermembrane space leads to increased recruitment of small heat shock proteins. Depletion of small heat shock proteins leads to mitochondrial swelling and reduced respiration, while aggregation of aggregation-prone substrates is countered in their presence. Charcot–Marie–Tooth disease-causing mutations disturb the mitochondrial function of HSPB1, potentially linking previously observed mitochondrial dysfunction in Charcot–Marie–Tooth type 2F to its role in the mitochondrial intermembrane space. Our results reveal that small heat shock proteins form a chaperone system that operates in the mitochondrial intermembrane space. Adriaenssens et al. provide evidence suggesting that cytosolic small heat shock proteins localize to the mitochondrial intermembrane space, where they operate as molecular chaperones.
登录
查看更多内容
光学成像。膨胀显微镜。
DOI：
10.1126/science.1260088
发表时间：
2015-01-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chen F;Tillberg PW;Boyden ES
通讯作者：
Boyden ES
影响因子：
5.6
作者：
Escobar MR;Feussner I;Valle EM
通讯作者：
Valle EM
DOI：
10.1074/jbc.m109.082644
发表时间：
2010-04-23
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Almeida-Souza L;Goethals S;de Winter V;Dierick I;Gallardo R;Van Durme J;Irobi J;Gettemans J;Rousseau F;Schymkowitz J;Timmerman V;Janssens S
通讯作者：
Janssens S
影响因子：
3.3
作者：
Baker, Michael J.;Webb, Chaille T.;Ryan, Michael T.
通讯作者：
Ryan, Michael T.
影响因子：
12.7
作者：
Bouhy, Delphine;Juneja, Manisha;Timmerman, Vincent
通讯作者：
Timmerman, Vincent