Details

Autor(en) / Beteiligte

• Baker, Brooke M
• Nargund, Amrita M
• Sun, Tiffany
• Haynes, Cole M
• Larsson, Nils-Göran

Titel

Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2

Ist Teil von

• PLoS genetics, 2012-06, Vol.8 (6), p.e1002760-e1002760

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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).