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Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt

Rolland, SG; Schneid, S; Schwarz, M; Rackles, E; Fischer, C; Haeussler, S; Regmi, SG; ... Conradt, B; + view all (2019) Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt. Cell Reports , 28 (7) 1659-1669.e5. 10.1016/j.celrep.2019.07.049. Green open access

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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.

Type: Article
Title: Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2019.07.049
Publisher version: https://doi.org/10.1016/j.celrep.2019.07.049
Language: English
Additional information: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: ATFS-1, C. elegans, GCN-2, UPR(mt), hsp-6, hsp-60, mitochondria
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10080122
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