Dataset Information

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

ABSTRACT: The metabolic plasticity of mitochondria supports cell development and differentiation and ensures cell survival under stress. The peptidase OMA1 regulates mitochondrial morphology and stress signaling and orchestrates tumorigenesis and cell fate decisions in a cell and tissue-specific manner. Here, we have used unbiased systemic approaches to demonstrate that OMA1-dependent cell fate decisions are under metabolic control. A metabolism-focus CRISPR screen combined with an integrated analysis of human expression data unraveled a protective role of OMA1 against DNA damage. Nucleotide deficiencies induced by chemotherapeutic agents promote the selective, p53-dependent apoptosis of cells lacking OMA1. The protective effect of OMA1 does not depend on OMA1 activation nor on OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells have reduced glycolytic capacity and accumulate OXPHOS proteins upon DNA damage. OXPHOS inhibition restores glycolysis and confers resistance against DNA damage. Thus, metabolic cues determine cell fate decisions by OMA1, which sheds new light on the role of OMA1 in cancerogenesis.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Hendrik Nolte

LAB HEAD: Thomas Langer

PROVIDER: PXD036595 | Pride | 2023-04-04

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	0140_SEARCH.zip	Other
	20210825_DD_0140_PaRi_wholeP_sample_01.raw	Raw
	20210825_DD_0140_PaRi_wholeP_sample_02.raw	Raw
	20210825_DD_0140_PaRi_wholeP_sample_03.raw	Raw
	20210825_DD_0140_PaRi_wholeP_sample_04.raw	Raw

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Publications

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

Rivera-Mejías Pablo P Narbona-Pérez Álvaro Jesús ÁJ Hasberg Lidwina L Kroczek Lara L Bahat Amir A Lawo Steffen S Folz-Donahue Kat K Schumacher Anna-Lena AL Ahola Sofia S Mayer Fiona Carola FC Giavalisco Patrick P Nolte Hendrik H Lavandero Sergio S Langer Thomas T

Cell reports 20230331 4

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 fo ...[more]

PMID: 37002921

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