[PDF][PDF] ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans
The cellular response to unfolded and misfolded proteins in the mitochondrial matrix is
poorly understood. Here, we report on a genome-wide RNAi-based screen for genes that
signal the mitochondrial unfolded protein response (UPR mt) in C. elegans. Unfolded
protein stress in the mitochondria correlates with complex formation between a
homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-
5, both of which are encoded by genes required for signaling the UPR mt. Activation of the …
poorly understood. Here, we report on a genome-wide RNAi-based screen for genes that
signal the mitochondrial unfolded protein response (UPR mt) in C. elegans. Unfolded
protein stress in the mitochondria correlates with complex formation between a
homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-
5, both of which are encoded by genes required for signaling the UPR mt. Activation of the …
Summary
The cellular response to unfolded and misfolded proteins in the mitochondrial matrix is poorly understood. Here, we report on a genome-wide RNAi-based screen for genes that signal the mitochondrial unfolded protein response (UPRmt) in C. elegans. Unfolded protein stress in the mitochondria correlates with complex formation between a homeodomain-containing transcription factor DVE-1 and the small ubiquitin-like protein UBL-5, both of which are encoded by genes required for signaling the UPRmt. Activation of the UPRmt correlates temporally and spatially with nuclear redistribution of DVE-1 and with its enhanced binding to the promoters of mitochondrial chaperone genes. These events and the downstream UPRmt are attenuated in animals with reduced activity of clpp-1, which encodes a mitochondrial matrix protease homologous to bacterial ClpP. As ClpP is known to function in the bacterial heat-shock response, our findings suggest that eukaryotes utilize component(s) from the protomitochondrial symbiont to signal the UPRmt.
cell.com