OMA1 reprograms metabolism under hypoxia to promote colorectal cancer development.

ABSTRACT: Many cancer cells maintain enhanced aerobic glycolysis due to irreversible defective mitochondrial oxidative phosphorylation (OXPHOS). This phenomenon, known as the Warburg effect, is recently challenged because most cancer cells maintain OXPHOS. However, how cancer cells coordinate glycolysis and OXPHOS remains largely unknown. Here, we demonstrate that OMA1, a stress-activated mitochondrial protease, promotes colorectal cancer development by driving metabolic reprogramming. OMA1 knockout suppresses colorectal cancer development in AOM/DSS and xenograft mice models of colorectal cancer. OMA1-OPA1 axis is activated by hypoxia, increasing mitochondrial ROS to stabilize HIF-1α, thereby promoting glycolysis in colorectal cancer cells. On the other hand, under hypoxia, OMA1 depletion promotes

SUBMITTER: Wu Z 

PROVIDER: S-EPMC7788456 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature