Longevity & AgingNew Protein LRRC58 Found to Control Cysteine Breakdown and Liver Cholesterol
Researchers developed Covariation MS — a technique combining proteomics and metabolomics in 163 genetically diverse mice — to map functional relationships between 11,868 proteins and 285 metabolites. This produced a Metabolite-Protein Covariation Architecture (MPCA) nominating 3,542 previously unknown protein-metabolite relationships. Using MPCA, they identified LRRC58, a poorly characterized protein, as the substrate adaptor of an E3 ubiquitin ligase that targets CDO1 — the rate-limiting enzyme converting cysteine to taurine — for proteasomal degradation. Cysteine abundance itself regulates this process. Depleting LRRC58 in mouse hepatocytes stabilizes CDO1, increases taurine production, and lowers hepatic cholesterol, as taurine promotes bile acid-mediated cholesterol excretion.
