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ULP-2 SUMO protease regulates UPRmt and mitochondrial homeostasis in Caenorhabditis elegans

Michaeli, Lirin; Spector, Eyal; Haeussler, Simon; Carvalho, Cátia A; Grobe, Hanna; Abu-Shach, Ulrike Bening; Zinger, Hen; ... Broday, Limor; + view all (2024) ULP-2 SUMO protease regulates UPRmt and mitochondrial homeostasis in Caenorhabditis elegans. Free Radical Biology and Medicine , 214 pp. 19-27. 10.1016/j.freeradbiomed.2024.01.050. Green open access

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Abstract

Mitochondria are the powerhouses of cells, responsible for energy production and regulation of cellular homeostasis. When mitochondrial function is impaired, a stress response termed mitochondrial unfolded protein response (UPRmt) is initiated to restore mitochondrial function. Since mitochondria and UPRmt are implicated in many diseases, it is important to understand UPRmt regulation. In this study, we show that the SUMO protease ULP-2 has a key role in regulating mitochondrial function and UPRmt. Specifically, down-regulation of ulp-2 suppresses UPRmt and reduces mitochondrial membrane potential without significantly affecting cellular ROS. Mitochondrial networks are expanded in ulp-2 null mutants with larger mitochondrial area and increased branching. Moreover, the amount of mitochondrial DNA is increased in ulp-2 mutants. Downregulation of ULP-2 also leads to alterations in expression levels of mitochondrial genes involved in protein import and mtDNA replication, however, mitophagy remains unaltered. In summary, this study demonstrates that ULP-2 is required for mitochondrial homeostasis and the UPRmt.

Type: Article
Title: ULP-2 SUMO protease regulates UPRmt and mitochondrial homeostasis in Caenorhabditis elegans
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.freeradbiomed.2024.01.050
Publisher version: http://dx.doi.org/10.1016/j.freeradbiomed.2024.01....
Language: English
Additional information: © 2024 The Authors. Published by Elsevier Inc. under a Creative Commons license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: SUMO, Smo-1, ULP-2, SUMO protease, SENP, Mitochondrial unfolded protein response, UPRmt
UCL classification: UCL
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-pp.ucl.ac.uk/id/eprint/10187532
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