美国麻省理工学院David M. Sabatini研究团队发现，MFSD12介导半胱氨酸进入黑素体和溶酶体。相关论文于2020年11月18日在线发表在《自然》杂志上。

Title: MFSD12 mediates the import of cysteine into melanosomes and lysosomes

Author: Charles H. Adelmann, Anna K. Traunbauer, Brandon Chen, Kendall J. Condon, Sze Ham Chan, Tenzin Kunchok, Caroline A. Lewis, David M. Sabatini

Issue&Volume: 2020-11-18

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 functions1,2. 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 humans3,4. 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 oxidation5,6. Tracing and biochemical analyses show that MFSD12 is necessary for the import of cysteine into melanosomes and, in non-pigmented cells, lysosomes. Indeed, loss of MFSD12 reduced the accumulation of cystine in lysosomes of fibroblasts from patients with cystinosis, a lysosomal-storage disease caused by inactivation of the lysosomal cystine exporter cystinosin7,8,9. Thus, MFSD12 is an essential component of the cysteine importer for melanosomes and lysosomes.

DOI: 10.1038/s41586-020-2937-x

Source: https://www.nature.com/articles/s41586-020-2937-x