RRC ID 46263
Author Baker BM, Nargund AM, Sun T, Haynes CM.
Title Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2.
Journal PLoS Genet
Abstract Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2-dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS) generated from dysfunctional mitochondria are required for GCN-2-dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPR(mt).
Volume 8(6)
Pages e1002760
Published 2012-1-1
DOI 10.1371/journal.pgen.1002760
PMID 22719267
PMC PMC3375257
MeSH ATP-Binding Cassette Transporters* / genetics ATP-Binding Cassette Transporters* / metabolism Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Mitochondria* / genetics Mitochondria* / metabolism Mitochondria* / pathology Molecular Chaperones Phosphorylation Protein Biosynthesis* / genetics Protein Folding Reactive Oxygen Species / metabolism Signal Transduction Stress, Physiological Transcription Factors* / genetics Transcription Factors* / metabolism Unfolded Protein Response eIF-2 Kinase / genetics eIF-2 Kinase / metabolism
IF 5.175
Times Cited 156
C.elegans tm4525