An OMA1 redox site controls mitochondrial homeostasis, sarcoma growth, and immunogenicity.

ABSTRACT: Aggressive tumors often display mitochondrial dysfunction. Upon oxidative stress, mitochondria undergo fission through OMA1-mediated cleavage of the fusion effector OPA1. In yeast, a redox-sensing switch participates in OMA1 activation. 3D modeling of OMA1 comforted the notion that cysteine 403 might participate in a similar sensor in mammalian cells. Using prime editing, we developed a mouse sarcoma cell line in which OMA1 cysteine 403 was mutated in alanine. Mutant cells showed impaired mitochondrial responses to stress including ATP production, reduced fission, resistance to apoptosis, and enhanced mitochondrial DNA release. This mutation prevented tumor development in immunocompetent, but not nude or cDC1 dendritic cell-deficient, mice. These cells prime CD8⁺ lymphocytes tha

SUBMITTER: Miallot R 

PROVIDER: S-EPMC10078952 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature