MitoStores: a place for precursors to ride out the storm

Abstract

The fate of unimported mitochondrial precursors has been increasingly studied in recent years, mostly focusing on protein degradation. In this issue of the EMBO journal, Krämer et al discovered MitoStores, a new protective mechanism that temporarily stores mitochondrial proteins in cytosolic deposits.

Figure 1. Quality control of unimported mitochondrial proteins

Posttranslationally translocated mitochondrial proteins are synthesized in the cytosol. Different pathways have evolved to respond to defects in the import of these precursors into mitochondria and to prevent cellular proteotoxicity. Certain mitochondrial proteins are promptly degraded by the proteosome. Two mechanisms regulate precursors containing a mitochondrial targeting signal (MTS): (i) mitoNUC—precursors are sequestered in nuclear inclusion bodies and subsequently degraded by the proteosome, (ii) MitoStores—Hsp104 and Hsp42 control the formation of mitochondria‐associated cytosolic inclusion bodies where precursors are temporarily stored. MitoStores‐sequestered precursors are translocated into mitochondria upon restoration of protein import capacity. Other quality control pathways for mitochondrial precursors such as carrier, outer membrane (OM), and intermembrane space (IMS) proteins are yet to be discovered. It is unclear whether these precursors are sequestered in different types of aggregates or regulated by other mechanisms.