Congratulations to Dylan, whose manuscript 'LRRC58 defines an E3 ubiquitin ligase complex sensitive to cysteine abundance' was uploaded to bioRxiv today.

How cells sense the abundance of many critical nutrients remains poorly defined. Supporting recent findings from the Chouchani Lab (https://www.nature.com/articles/s41586-025-09535-5) Dylan has identified a Cullin-RING E3 ligase complex containing the uncharacterised substrate receptor LRRC58 as a new regulator of cysteine metabolism. It achieves this by degrading CDO1, the key enzyme responsible for cysteine breakdown, when cysteine is scarce. Conditionality is imparted at the level of LRRC58 stability: when cysteine is abundant, LRRC58 is itself degraded; when cysteine is scarce, LRRC58 accumulates and targets CDO1 for degradation. The physiological importance of the LRRC58-mediated regulation of CDO1 is underscored by the recent identification of dominant mutations in CDO1 in children with severe neurodevelopmental defects. Dylan's work shows that these mutations prevent LRRC58 binding, thus encoding dominant-active proteins free to catabolise cysteine unrestrained by negative regulation via LRRC58.

The full preprint can be found at https://www.biorxiv.org/content/10.1101/2025.09.23.678073v1.

We are very grateful to our collaborators in the Ciulli Lab (CeTPD, Dundee), the Bayin Lab (Gurdon Institute), the Weekes Lab (CIMR, Cambridge) and the Tchasovnikarova Lab (Gurdon Institute).