title: Signaling the mitochondrial unfolded protein response.
abstract: Mitochondria are compartmentalized organelles essential for numerous cellular functions including ATP generation, iron-sulfur cluster biogenesis, nucleotide and amino acid metabolism as well as apoptosis. To promote biogenesis and proper function, mitochondria have a dedicated repertoire of molecular chaperones to facilitate protein folding and quality control proteases to degrade those proteins that fail to fold correctly. Mitochondrial protein folding is challenged by the complex organelle architecture, the deleterious effects of electron transport chain-generated reactive oxygen species and the mitochondrial genome's susceptibility to acquiring mutations. In response to the accumulation of unfolded or misfolded proteins beyond the organelle's chaperone capacity, cells mount a mitochondrial unfolded protein response (UPR(mt)). The UPR(mt) is a mitochondria-to-nuclear signal transduction pathway resulting in the induction of mitochondrial protective genes including mitochondrial molecular chaperones and proteases to re-establish protein homeostasis within the mitochondrial protein-folding environment. Here, we review the current understanding of UPR(mt) signal transduction and the impact of the UPR(mt) on diseased cells. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids.
authors.affiliation: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Pellegrino
authors.forename: Amrita M
authors.initials: AM
authors.lastname: Nargund
authors.forename: Cole M
authors.initials: CM
authors.lastname: Haynes
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D029742:Caenorhabditis elegans Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones