Sorting out how Msp1 maintains mitochondrial membrane proteostasis

Abstract

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.

Keywords: AAA; Mitochondria; Msp1; Proteostasis; Tail-anchored.