Published March 14, 2023 | Version v1
Dataset Open

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

Description

The provided Dataset contains the liquid-chromatography mass spectrometry (LC-MS) raw files (3 zipped files containing the Thermo .raw files) and one zipped file containing three tables extracted containing the peak information (Compound ID, expected RT (min), Filename, Injection Volume (uL), peak height, peak area, actual RT (min), RT Delta, formula, adduct, m/z (Expected), m/z (Apex), m/z (Delta in ppm) and S/N (signa-to-noise)) of the steady state and the 13C6 glucose-traced metabolite measurements for the above mentioned (see title) publication in Cell Reports.

The data was measured using either anion-chromatography coupled to high resolution mass spectrometry (for anionic compounds, including intermediates from the TCA cycle, glycolysis, pentose phosphate pathway and nucleotides) or ultra high performance liquid chromatography coupled to high resolution mass spectrometry (amine-containing compounds, including amino acids and polyamines). The methods used for extracting and analyzing the samples are described in detail in the above mentioned publication. The data deposited here is shown in figure 7a and b and figure S7a, b and c.

 

 

Notes

Summary of the paper: 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 demonstrate that OMA1-dependent cell survival depends on metabolic cues. A metabolism-focused CRISPR screen combined with an integrated analysis of human gene expression data unravels 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 nor OMA1-mediated OPA1 and DELE1 processing. OMA1-deficient cells show reduced glycolysis and accumulate 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.

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