MDH2 regulates the sensitivity of clear cell renal cell carcinoma to ferroptosis through its interaction with FSP1.

ABSTRACT: Malate dehydrogenase 2 is a pivotal enzyme in the tricarboxylic acid cycle. Recent studies have highlighted the significant involvement of MDH2 in the pathogenesis and progression of diverse types of tumors, yet its precise mechanistic underpinnings remain elusive. This study revealed a significant decrease in MDH2 expression in renal cancer tissues. And knocking out MDH2 was observed to hinder the proliferation of normal renal tubular epithelial cells but notably enhance the proliferation of ccRCC. Furthermore, mechanistically, we found that MDH2 inhibits the proliferation of ccRCC by promoting ferroptosis, while enhancing the sensitivity of ccRCC to ferroptosis inducers, promoting lipid peroxidation. We also demonstrated that MDH2 regulates the ubiquitination of FSP1 through protein-prot

SUBMITTER: Feng B 

PROVIDER: S-EPMC11322664 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature