Department of Chemistry & Biochemistry, University of Toledo, Toledo, OH 43606, USA.
Department of Chemistry & Biochemistry, University of Toledo, Toledo, OH 43606, USA.
Mitochondrion. 2019 Nov;49:128-134. doi: 10.1016/j.mito.2019.07.011. Epub 2019 Aug 5.
Robust membrane proteostasis networks are essential for cells to withstand proteotoxic stress arising from environmental insult and intrinsic errors in protein production (Labbadia and Morimoto, 2015; Hegde and Zavodszky, 2019). Failures in mitochondrial membrane proteostasis are associated with cancer, aging, and a range of cardiovascular and neurodegenerative diseases (Wallace et al., 2010; Martin, 2012; Gustafsson and Gottlieb, 2007). As a result, mitochondria possess numerous pathways to maintain proteostasis (Avci and Lemberg, 2015; Shi et al., 2016; Weidberg and Amon, 2018; Shpilka and Haynes, 2018; Quirós et al., 2016; Sorrentino et al., 2017). Mitochondrial Sorting of Proteins 1 (Msp1) is a membrane anchored AAA ATPase that extracts proteins from the outer mitochondrial membrane (OMM) (Chen et al., 2014; Okreglak and Walter, 2014). In the past few years, several papers have addressed various aspects of Msp1 function. Here, we summarize these recent advances to build a basic model for how Msp1 maintains mitochondrial membrane proteostasis while also highlighting outstanding questions in the field.
稳健的膜蛋白稳态网络对于细胞耐受由环境损伤和蛋白质产生内在错误引起的蛋白毒性应激至关重要（Labbadia 和 Morimoto，2015；Hegde 和 Zavodszky，2019）。线粒体膜蛋白稳态的失败与癌症、衰老以及一系列心血管和神经退行性疾病有关（Wallace 等人，2010；Martin，2012；Gustafsson 和 Gottlieb，2007）。因此，线粒体拥有多种维持蛋白稳态的途径（Avci 和 Lemberg，2015；Shi 等人，2016；Weidberg 和 Amon，2018；Shpilka 和 Haynes，2018；Quirós 等人，2016；Sorrentino 等人，2017）。线粒体蛋白分选 1（Msp1）是一种膜锚定的 AAA ATP 酶，可从外线粒体膜（OMM）中提取蛋白质（Chen 等人，2014；Okreglak 和 Walter，2014）。在过去的几年中，有几篇论文探讨了 Msp1 功能的各个方面。在这里，我们总结了这些最新进展，以构建一个基本模型，说明 Msp1 如何维持线粒体膜蛋白稳态，同时突出该领域的未解决问题。
