ULP-2 SUMO protease regulates UPR mt and mitochondrial homeostasis in Caenorhabditis elegans.

Autor: Michaeli L; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Spector E; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Haeussler S; Faculty of Biology, Ludwig-Maximilians-University Munich, Munich, Germany., Carvalho CA; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Grobe H; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Abu-Shach UB; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Zinger H; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel., Conradt B; Faculty of Biology, Ludwig-Maximilians-University Munich, Munich, Germany; Department of Cell and Developmental Biology, Division of Biosciences, University College London, London, United Kingdom., Broday L; Department of Cell and Developmental Biology, School of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel. Electronic address: broday@tauex.tau.ac.il.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2024 Mar; Vol. 214, pp. 19-27. Date of Electronic Publication: 2024 Jan 30.
DOI: 10.1016/j.freeradbiomed.2024.01.050
Abstrakt: 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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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