线粒体的代谢可塑性确保细胞发育、分化和存活。肽酶OMA1通过OPA1调节线粒体形态，并通过DELE1调节压力信号，在细胞和组织特异性中协调肿瘤发生和细胞存活。在这里，我们使用公正的系统基础方法表明，OMA1依赖代谢提示来促进细胞存活。代谢关注CRISPR筛选结合人类基因表达数据的集成分析发现，OMA1可以保护免受DNA损伤。化疗药物诱导的核苷酸缺乏促进缺乏OMA1的细胞p53依赖性细胞凋亡。OMA1的保护作用不依赖于OMA1激活或OMA1介导的OPA1和DELE1处理。OMA1缺陷细胞在DNA损伤下显示出减少的糖酵解和积累的氧化磷酸化（OXPHOS）蛋白。OXPHOS抑制恢复糖酵解并赋予抵抗DNA损伤的能力。因此，OMA1通过控制葡萄糖代谢来决定细胞死亡和存活之间的平衡，阐明了它在癌症发生中的作用。版权所有©2023年作者。由Elsevier Inc.出版。保留所有权利。

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.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.