MFSD12 mediates the import of cysteine into melanosomes and lysosomes

Charles H. Adelmann, Anna K. Traunbauer, Brandon Chen, Kendall J. Condon, Sze Ham Chan, Tenzin Kunchok, Caroline A. Lewis and David M. Sabatini ()
Additional contact information
Charles H. Adelmann: Massachusetts Institute of Technology
Anna K. Traunbauer: Massachusetts Institute of Technology
Brandon Chen: Massachusetts Institute of Technology
Kendall J. Condon: Massachusetts Institute of Technology
Sze Ham Chan: Massachusetts Institute of Technology
Tenzin Kunchok: Massachusetts Institute of Technology
Caroline A. Lewis: Massachusetts Institute of Technology
David M. Sabatini: Massachusetts Institute of Technology

Nature, 2020, vol. 588, issue 7839, 699-704

Abstract: 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 cystinosin7–9. Thus, MFSD12 is an essential component of the cysteine importer for melanosomes and lysosomes.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2937-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:588:y:2020:i:7839:d:10.1038_s41586-020-2937-x

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2937-x

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().