Mitochondrial reprogramming by activating OXPHOS via glutamine metabolism in African American patients with bladder cancer.

ABSTRACT: Bladder cancer (BLCA) mortality is higher in African American (AA) patients compared with European American (EA) patients, but the molecular mechanism underlying race-specific differences are unknown. To address this gap, we conducted comprehensive RNA-Seq, proteomics, and metabolomics analysis of BLCA tumors from AA and EA. Our findings reveal a distinct metabolic phenotype in AA BLCA characterized by elevated mitochondrial oxidative phosphorylation (OXPHOS), particularly through the activation of complex I. The results provide insight into the complex I activation-driven higher OXPHOS activity resulting in glutamine-mediated metabolic rewiring and increased disease progression, which was also confirmed by [U]13C-glutamine tracing. Mechanistic studies further demonstrate that knockdown of

SUBMITTER: Kami Reddy KR 

PROVIDER: S-EPMC11385078 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature