7-Dehydrocholesterol dictates ferroptosis sensitivity.

ABSTRACT: Ferroptosis, a form of regulated cell death that is driven by iron-dependent phospholipid peroxidation, has been implicated in multiple diseases, including cancer^1-3, degenerative disorders⁴ and organ ischaemia-reperfusion injury (IRI)^5,6. Here, using genome-wide CRISPR-Cas9 screening, we identified that the enzymes involved in distal cholesterol biosynthesis have pivotal yet opposing roles in regulating ferroptosis through dictating the level of 7-dehydrocholesterol (7-DHC)-an intermediate metabolite of distal cholesterol biosynthesis that is synthesized by sterol C5-desaturase (SC5D) and metabolized by 7-DHC reductase (DHCR7) for cholesterol synthesis. We found that the pathway components, including MSMO1, CYP51A1, EBP and SC5D, function as potential supp

SUBMITTER: Li Y 

PROVIDER: S-EPMC11298758 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature