MFSD12 mediates the import of cysteine into melanosomes and lysosomes

  • 1.

    Basrur, V. et al. Proteomic analysis of early melanosomes: identification of novel melanosomal proteins. J. Proteome Res. 2, 69–79 (2003).

    ADS  CAS  Article  Google Scholar 

  • 2.

    Sturm, R. A. Molecular genetics of human pigmentation diversity. Hum. Mol. Genet. 18 (R1), R9–R17 (2009).

    CAS  Article  Google Scholar 

  • 3.

    Adhikari, K. et al. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia. Nat. Commun. 10, 358 (2019).

    ADS  Article  Google Scholar 

  • 4.

    Crawford, N. G. et al. Loci associated with skin pigmentation identified in African populations. Science 358, eaan8433 (2017).

    Article  Google Scholar 

  • 5.

    D’Alba, L. & Shawkey, M. D. Melanosomes: biogenesis, properties, and evolution of an ancient organelle. Physiol. Rev. 99, 1–19 (2019).

    Article  Google Scholar 

  • 6.

    Prota, G. Melanins and Melanogenesis (Academic, 1992).

  • 7.

    Gahl, W. A., Bashan, N., Tietze, F., Bernardini, I. & Schulman, J. D. Cystine transport is defective in isolated leukocyte lysosomes from patients with cystinosis. Science 217, 1263–1265 (1982).

    ADS  CAS  Article  Google Scholar 

  • 8.

    Jonas, A. J., Smith, M. L. & Schneider, J. A. ATP-dependent lysosomal cystine efflux is defective in cystinosis. J. Biol. Chem. 257, 13185–13188 (1982).

    CAS  PubMed  Google Scholar 

  • 9.

    Town, M. et al. A novel gene encoding an integral membrane protein is mutated in nephropathic cystinosis. Nat. Genet. 18, 319–324 (1998).

    CAS  Article  Google Scholar 

  • 10.

    Watabe, H., Kushimoto, T., Valencia, J. C. & Hearing, V. J. in Current Protocols in Cell Biology (eds J. S. Bonifacino et al.) (John Wiley & Sons, 2005).

  • 11.

    Abu-Remaileh, M. et al. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science 358, 807–813 (2017).

    ADS  CAS  Article  Google Scholar 

  • 12.

    Chen, W. W., Freinkman, E., Wang, T., Birsoy, K. & Sabatini, D. M. Absolute quantification of matrix metabolites reveals the dynamics of mitochondrial metabolism. Cell 166, 1324–1337 (2016).

    CAS  Article  Google Scholar 

  • 13.

    Ray, G. J. et al. A PEROXO-tag enables rapid isolation of peroxisomes from human cells. iScience 23, 101109 (2020).

    ADS  CAS  Article  Google Scholar 

  • 14.

    Bruder, J. M. et al. Melanosomal dynamics assessed with a live-cell fluorescent melanosomal marker. PLoS ONE 7, e43465 (2012).

    ADS  CAS  Article  Google Scholar 

  • 15.

    Diment, S., Eidelman, M., Rodriguez, G. M. & Orlow, S. J. Lysosomal hydrolases are present in melanosomes and are elevated in melanizing cells. J. Biol. Chem. 270, 4213–4215 (1995).

    CAS  Article  Google Scholar 

  • 16.

    Bissig, C., Rochin, L. & van Niel, G. PMEL amyloid fibril formation: the bright steps of pigmentation. Int. J. Mol. Sci. 17, 1438 (2016).

    Article  Google Scholar 

  • 17.

    Reddy, V. S., Shlykov, M. A., Castillo, R., Sun, E. I. & Saier, M. H. Jr. The major facilitator superfamily (MFS) revisited. FEBS J. 279, 2022–2035 (2012).

    CAS  Article  Google Scholar 

  • 18.

    Bloom, J. L. & Falconer, D. S. ‘Grizzled’, a mutant in linkage group X of the mouse. Genet. Res. 7, 159–167 (1966).

    Article  Google Scholar 

  • 19.

    Potterf, S. B. et al. Cysteine transport in melanosomes from murine melanocytes. Pigment Cell Res. 12, 4–12 (1999).

    CAS  Article  Google Scholar 

  • 20.

    Kawaji, H., Kasukawa, T., Forrest, A., Carninci, P. & Hayashizaki, Y. The FANTOM5 collection, a data series underpinning mammalian transcriptome atlases in diverse cell types. Sci. Data 4, 170113 (2017).

    CAS  Article  Google Scholar 

  • 21.

    Uhlén, M. et al. Tissue-based map of the human proteome. Science 347, 1260419 (2015).

    Article  Google Scholar 

  • 22.

    Pisoni, R. L., Acker, T. L., Lisowski, K. M., Lemons, R. M. & Thoene, J. G. A cysteine-specific lysosomal transport system provides a major route for the delivery of thiol to human fibroblast lysosomes: possible role in supporting lysosomal proteolysis. J. Cell Biol. 110, 327–335 (1990).

    CAS  Article  Google Scholar 

  • 23.

    Gahl, W. A., Thoene, J. G. & Schneider, J. A. Cystinosis. N. Engl. J. Med. 347, 111–121 (2002).

    Article  Google Scholar 

  • 24.

    Oshima, R. G., Rhead, W. J., Thoene, J. G. & Schneider, J. A. Cystine metabolism in human fibroblasts. Comparison of normal, cystinotic, and gamma-glutamylcysteine synethetase-deficient cells. J. Biol. Chem. 251, 4287–4293 (1976).

    CAS  PubMed  Google Scholar 

  • 25.

    Sato, H., Tamba, M., Ishii, T. & Bannai, S. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274, 11455–11458 (1999).

    CAS  Article  Google Scholar 

  • 26.

    Wilbrandt, W. & Rosenberg, T. The concept of carrier transport and its corollaries in pharmacology. Pharmacol. Rev. 13, 109–183 (1961).

    CAS  PubMed  Google Scholar 

  • 27.

    Behnke, J., Eskelinen, E.-L., Saftig, P. & Schröder, B. Two dileucine motifs mediate late endosomal/lysosomal targeting of transmembrane protein 192 (TMEM192) and a C-terminal cysteine residue is responsible for disulfide bond formation in TMEM192 homodimers. Biochem. J. 434, 219–231 (2011).

    CAS  Article  Google Scholar 

  • 28.

    Lloyd, J. B. Disulphide reduction in lysosomes. The role of cysteine. Biochem. J. 237, 271–272 (1986).

    CAS  Article  Google Scholar 

  • 29.

    Mego, J. L. Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin. Biochem. J. 218, 775–783 (1984).

    CAS  Article  Google Scholar 

  • 30.

    Tsui, C. K. et al. CRISPR–cas9 screens identify regulators of antibody-drug conjugate toxicity. Nat. Chem. Biol. 15, 949–958 (2019).

    CAS  Article  Google Scholar 

  • 31.

    Gahl, W. A. et al. Cysteamine therapy for children with nephropathic cystinosis. N. Engl. J. Med. 316, 971–977 (1987).

    CAS  Article  Google Scholar 

  • 32.

    Thoene, J. G., Oshima, R. G., Crawhall, J. C., Olson, D. L. & Schneider, J. A. Cystinosis. Intracellular cystine depletion by aminothiols in vitro and in vivo. J. Clin. Invest. 58, 180–189 (1976).

    CAS  Article  Google Scholar 

  • 33.

    Mujahid, N. et al. A UV-independent topical small-molecule approach for melanin production in human skin. Cell Rep. 19, 2177–2184 (2017).

    CAS  Article  Google Scholar 

  • 34.

    Djoumbou-Feunang, Y. et al. CFM-ID 3.0: significantly improved ESI-MS/MS prediction and compound identification. Metabolites 9, 72 (2019).

    CAS  Article  Google Scholar 

  • 35.

    Wishart, D. S. et al. HMDB: the Human Metabolome Database. Nucleic Acids Res. 35, D521–D526 (2007).

    CAS  Article  Google Scholar 

  • 36.

    Guan, X., Hoffman, B., Dwivedi, C. & Matthees, D. P. A simultaneous liquid chromatography/mass spectrometric assay of glutathione, cysteine, homocysteine and their disulfides in biological samples. J. Pharm. Biomed. Anal. 31, 251–261 (2003).

    CAS  Article  Google Scholar 

  • 37.

    Martin, G. B. et al. Development of a mass spectrometry method for the determination of a melanoma biomarker, 5-S-cysteinyldopa, in human plasma using solid phase extraction for sample clean-up. J. Chromatogr. A 1156, 141–148 (2007).

    CAS  Article  Google Scholar 

  • 38.

    Ito, S. & Prota, G. A facile one-step synthesis of cysteinyldopas using mushroom tyrosinase. Experientia 33, 1118–1119 (1977).

    CAS  Article  Google Scholar 

  • 39.

    Graham, J. M. Isolation of lysosomes from tissues and cells by differential and density gradient centrifugation. Curr. Protoc. Cell Biol. Ch. 3, Unit 3.6 (2001).

    Google Scholar 

  • 40.

    Goldman, R. & Kaplan, A. Rupture of rat liver lysosomes mediated by l-amino acid esters. Biochim. Biophys. Acta 318, 205–216 (1973).

    CAS  Article  Google Scholar 

  • 41.

    Verdon, Q. et al. SNAT7 is the primary lysosomal glutamine exporter required for extracellular protein-dependent growth of cancer cells. Proc. Natl Acad. Sci. USA 114, E3602–E3611 (2017).

    CAS  Article  Google Scholar 

  • Leave a Reply