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Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt

Authors: Stéphane G. Rolland; Sandra Schneid; Melanie Schwarz; Elisabeth Rackles; Christian Fischer; Simon Haeussler; Saroj G. Regmi; +5 Authors

Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt

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.

Keywords

QH301-705.5, Mitochondrial Proteins, Stress, Physiological, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], GCN-2, hsp-6, Animals, Biology (General), hsp-60, Caenorhabditis elegans, Caenorhabditis elegans Proteins, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Membrane Potential, Mitochondrial, C. elegans, ATFS-1, Mitochondria, mitochondria, [SDV] Life Sciences [q-bio], Protein Transport, UPR(mt), Unfolded Protein Response, Calcium, Protein Kinases, Transcription Factors

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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
142
Top 1%
Top 10%
Top 1%
Green
gold