MFSD12 mediates the import of cysteine into melanosomes and lysosomes.

ABSTRACT: Dozens of genes contribute to the wide variation in human pigmentation. Many of these genes encode proteins that localize to the melanosome-the organelle, related to the lysosome, that synthesizes pigment-but have unclear functions^1,2. Here we describe MelanoIP, a method for rapidly isolating melanosomes and profiling their labile metabolite contents. We use this method to study MFSD12, a transmembrane protein of unknown molecular function that, when suppressed, causes darker pigmentation in mice and humans^3,4. We find that MFSD12 is required to maintain normal levels of cystine-the oxidized dimer of cysteine-in melanosomes, and to produce cysteinyldopas, the precursors of pheomelanin synthesis made in melanosomes via cysteine oxidation^5,6. Tracing and bioc

SUBMITTER: Adelmann CH 

PROVIDER: S-EPMC7770032 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature