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

   

Authors:	Baker, B. M.; Nargund, A. M.; Sun, T.; Haynes, C. M.
Article Title:	Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2
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. © 2012 Baker et al.
Keywords:	signal transduction; controlled study; protein expression; protein phosphorylation; unclassified drug; genetics; nonhuman; protein function; animal; metabolism; animals; atp-binding cassette transporters; stress, physiological; protein depletion; transcription factor; rna interference; pathology; enzyme activity; phosphorylation; physiology; animalia; transcription factors; protein synthesis; abc transporter; reactive oxygen species; reactive oxygen metabolite; protein biosynthesis; caenorhabditis elegans; protein folding; mitochondria; cell protection; mitochondrion; cell stress; intracellular signaling; chaperone; disorders of mitochondrial functions; caenorhabditis elegans protein; caenorhabditis elegans proteins; molecular chaperones; unfolded protein response; life extension; translation regulation; initiation factor 2alpha; protein kinase r; eif-2 kinase; activating transcription factor associated with stress 1 protein; transcription factor gcn2; atfs 1 protein, c elegans; atfs-1 protein, c elegans; haf 1 protein, c elegans; haf-1 protein, c elegans; physiological stress
Journal Title:	PLoS Genetics
Volume:	8
Issue:	6
ISSN:	1553-7390
Publisher:	Public Library of Science
Date Published:	2012-06-08
Start Page:	e1002760
Language:	English
DOI:	10.1371/journal.pgen.1002760
PROVIDER:	scopus
PMCID:	PMC3375257
PUBMED:	22719267
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84864065342&partnerID=40&md5=f74709c35853b2c27c6c1f252ebb44ac
Notes:	--- - "Export Date: 1 August 2012" - "Source: Scopus"

https://synapse.mskcc.org/synapse/works/has_related_data_chk/31799