Tumour mitochondrial DNA mutations drive aerobic glycolysis to enhance checkpoint blockade.

ABSTRACT: The mitochondrial genome encodes essential machinery for respiration and metabolic homeostasis but is paradoxically among the most common targets of somatic mutation in the cancer genome, with truncating mutations in respiratory complex I genes being most over-represented¹. While mitochondrial DNA (mtDNA) mutations have been associated with both improved and worsened prognoses in several tumour lineages^1-3, whether these mutations are drivers or exert any functional effect on tumour biology remains controversial. Here we discovered that complex I-encoding mtDNA mutations are sufficient to remodel the tumour immune landscape and therapeutic resistance to immune checkpoint blockade. Using mtDNA base editing technology⁴ we engineered recurrent truncating mutat

SUBMITTER: Mahmood M 

PROVIDER: S-EPMC10055208 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature