Cooperation of protein machineries in mitochondrial protein sorting

Abstract

The function of mitochondria depends on the import of proteins, which are synthesized as precursors on cytosolic ribosomes. The majority of the precursor proteins are sorted into the mitochondrial subcompartments via five distinct routes. Recent studies revealed that molecular cooperation between protein machineries is a central feature of mitochondrial protein biogenesis. First, coupling to various partner proteins affects the substrate specificity of translocases and single translocation steps. Second, there is a substantial cooperation between different protein translocases in the import of specific precursor proteins. Third, protein transport is intimately linked to processing, folding and assembly reactions. Fourth, sorting of precursor proteins is functionally and physically connected to protein machineries, which fulfill central functions for respiration, maintenance of membrane architecture and form contacts to the endoplasmic reticulum. Therefore, we propose that the protein transport systems are part of a complicated protein network for mitochondrial biogenesis.

The mitochondrial BK Ca channel cardiac interactome reveals BK Ca association with the mitochondrial import receptor subunit Tom22, and the adenine nucleotide translocator

“…Specifically, we found the receptor proteins Tom22 and Tom70, and the protein-conducting channel Tom40 of the outer membrane TOM complex (Wenz et al, 2015); and Tim23, Tim16, GrpE1, and MPPA of the inner membrane Tim23-PAM classical presequence import pathway (Schulz et al, 2015). Although BK Ca lacks a presequence, there is precedence in the literature for atypical proteins (e.g.…”

Localized translation near the mitochondrial outer membrane: An update

“…Studies in the last 4 decades have shown that proteins can be imported following their complete synthesis by cytosolic ribosomes (i.e., post-translationally). 33,34 This suggested that mitochondria-destined proteins are translated throughout the cytoplasm and targeted to the mitochondria with the help of cytosolic chaperones that maintain them in an unfolded state. However, in the last decade, various lines of evidence have revived older models that propose the co-existence of localized translation near the mitochondria.…”

Mia40 is a facile oxidant of unfolded reduced proteins but shows minimal isomerase activity

“…In view of the general lack of substrate specificity observed in this work, all proteins transiting the IMS en route to their final location are potential substrates of the Mia40/lfALR system. However oxidation might be prevented by efficient sequestration during interactions with translocases [12, 13, 59] or chaperones [59, 60], or might be reversed via IMS-resident reductase sytems [23, 61–63]. In terms of an expanding role for the Mia40/lfALR system, it is interesting to note that a mitochondrial matrix protein Mrp10 contains two disulfide bonds that are inserted during transit through the IMS [34].…”