RRC ID 59584
Author Rolland SG, Schneid S, Schwarz M, Rackles E, Fischer C, Haeussler S, Regmi SG, Yeroslaviz A, Habermann B, Mokranjac D, Lambie E, Conradt B.
Title Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt.
Journal Cell Rep
Abstract The induction of the mitochondrial unfolded protein response (UPRmt) results in increased transcription of the gene encoding the mitochondrial chaperone HSP70. We systematically screened the C. elegans genome and identified 171 genes that, when knocked down, induce the expression of an hsp-6 HSP70 reporter and encode mitochondrial proteins. These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented). Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence, decreased protein import into mitochondria. In addition, it induces UPRmt in a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPRmt and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.
Volume 28(7)
Pages 1659-1669.e5
Published 2019-8-13
DOI 10.1016/j.celrep.2019.07.049
PII S2211-1247(19)30953-2
PMID 31412237
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism* Membrane Potential, Mitochondrial Mitochondria / metabolism* Mitochondria / pathology Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism* Protein Kinases / genetics Protein Kinases / metabolism* Protein Transport Stress, Physiological Transcription Factors / genetics Transcription Factors / metabolism* Unfolded Protein Response*
IF 7.815
Times Cited 16
C.elegans tm1779 tm4525