Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators

Abstract

Mitochondria are key components of eukaryotic cells, so their proper functioning is monitored via different mitochondrial signalling responses. One of these mitochondria-to-nuclear 'retrograde' responses to maintain mitochondrial homeostasis is the mitochondrial unfolded protein response (UPR^mt), which can be activated by a variety of defects including blocking mitochondrial translation, respiration, protein import or transmembrane potential. Although UPR^mt was first reported in cultured mammalian cells, this signalling pathway has also been extensively studied in the nematode Caenorhabditis elegans. In yeast, there are no published studies focusing on UPR^mt in a strict sense, but other unfolded protein responses (UPR) that appear related to UPR^mt have been described, such as the UPR activated by protein mistargeting (UPR^am) and mitochondrial compromised protein import response (mitoCPR). In plants, very little is known about UPR^mt and only recently some of the regulators have been identified. In this paper, we summarise and compare the current knowledge of the UPR^mt and related responses across eukaryotic kingdoms: animals, fungi and plants. Our comparison suggests that each kingdom has evolved its own specific set of regulators, however, the functional categories represented among UPR^mt-related target genes appear to be largely overlapping. This indicates that the strategies for preserving proper mitochondrial functions are partially conserved, targeting mitochondrial chaperones, proteases, import components, dynamics and stress response, but likely also non-mitochondrial functions including growth regulators/hormone balance and amino acid metabolism. We also identify homologs of known UPR^mt regulators and responsive genes across kingdoms, which may be interesting targets for future research.

Keywords: Mitochondria; Retrograde signalling; UPR(am); UPR(mt); Unfolded protein response; mitoCPR.