The mitochondrial protease OMA1 acts as a metabolic safeguard upon nuclear DNA damage.

Autor:	Rivera-Mejías P; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Center for Advanced Chronic Diseases (ACCDiS), Faculty of Chemical and Pharmaceutical Sciences & Faculty of Medicine, University of Chile, Santiago 8380492, Chile., Narbona-Pérez ÁJ; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Hasberg L; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Kroczek L; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Bahat A; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Lawo S; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Folz-Donahue K; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Schumacher AL; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Ahola S; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Mayer FC; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Giavalisco P; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Nolte H; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany., Lavandero S; Center for Advanced Chronic Diseases (ACCDiS), Faculty of Chemical and Pharmaceutical Sciences & Faculty of Medicine, University of Chile, Santiago 8380492, Chile; Cardiology Division, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA., Langer T; Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany. Electronic address: tlanger@age.mpg.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Apr 25; Vol. 42 (4), pp. 112332. Date of Electronic Publication: 2023 Mar 31.
DOI:	10.1016/j.celrep.2023.112332
Abstrakt:	The metabolic plasticity of mitochondria ensures cell development, differentiation, and survival. The peptidase OMA1 regulates mitochondrial morphology via OPA1 and stress signaling via DELE1 and orchestrates tumorigenesis and cell survival in a cell- and tissue-specific manner. Here, we use unbiased systems-based approaches to show that OMA1-dependent cell survival depends on metabolic cues. A metabolism-focused CRISPR screen combined with an integrated analysis of human gene expression data found that OMA1 protects against DNA damage. Nucleotide deficiencies induced by chemotherapeutic agents promote p53-dependent apoptosis of cells lacking OMA1. The protective effect of OMA1 does not depend on OMA1 activation or OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells show reduced glycolysis and accumulate oxidative phosphorylation (OXPHOS) proteins upon DNA damage. OXPHOS inhibition restores glycolysis and confers resistance against DNA damage. Thus, OMA1 dictates the balance between cell death and survival through the control of glucose metabolism, shedding light on its role in cancerogenesis. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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