title: The mucolipin-1 (TRPML1) ion channel, transmembrane-163 (TMEM163) protein, and lysosomal zinc handling.
abstract: Lysosomes are emerging as important players in cellular zinc ion (Zn2+) homeostasis. The series of work on Zn2+ accumulation in the neuronal lysosomes and the mounting evidence on the role of lysosomal Zn2+in cell death during mammary gland involution set a biological precedent for the central role of the lysosomes in cellular Zn2+handling. Such a role appears to involve cytoprotection on the one hand, and cell death on the other. The recent series of work began to identify the molecular determinants of the lysosomal Zn2+handling. In addition to zinc transporters (ZnT) of the solute-carrier family type 30A (SLC30A), the lysosomal ion channel TRPML1 and the poorly understood novel transporter TMEM163 have been shown to play a role in the Zn2+uptake by the lysosomes. In this review, we summarize the current knowledge on molecular determinants of the lysosomal Zn2+handling, uptake, and release pathways, as well as discuss their possible roles in health and disease.
authors.affiliation: Department of Biological Science, and Center for Applied Biotechnology Studies, California State University Fullerton, Fullerton, CA, 92831, USA.
authors.forename: Math P
authors.initials: MP
authors.lastname: Cuajungco
authors.affiliation: Dept. of Biological Sciences, University of Pittsburgh, 519 Langley Hall, 4249 Fifth Avenue, Pittsburgh, PA 15260, USA, kiselyov@pitt.edu.
authors.forename: Kirill
authors.initials: K
authors.lastname: Kiselyov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D017136:Ion Transport; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
chemical_list: C416674:MCOLN1 protein, human; D008565:Membrane Proteins; C579751:TMEM163 protein, human; D050051:Transient Receptor Potential Channels; D015032:Zinc