title: TRPML: transporters of metals in lysosomes essential for cell survival?
abstract: Key aspects of lysosomal function are affected by the ionic content of the lysosomal lumen and, therefore, by the ion permeability in the lysosomal membrane. Such functions include regulation of lysosomal acidification, a critical process in delivery and activation of the lysosomal enzymes, release of metals from lysosomes into the cytoplasm and the Ca(2+)-dependent component of membrane fusion events in the endocytic pathway. While the basic mechanisms of lysosomal acidification have been largely defined, the lysosomal metal transport system is not well understood. TRPML1 is a lysosomal ion channel whose malfunction is implicated in the lysosomal storage disease Mucolipidosis Type IV. Recent evidence suggests that TRPML1 is involved in Fe(2+), Ca(2+) and Zn(2+) transport across the lysosomal membrane, ascribing novel physiological roles to this ion channel, and perhaps to its relatives TRPML2 and TRPML3 and illuminating poorly understood aspects of lysosomal function. Further, alterations in metal transport by the TRPMLs due to mutations or environmental factors may contribute to their role in the disease phenotype and cell death.
authors.affiliation: Department of Biological Science, University of Pittsburgh, Pittsburgh, PA 15260, USA. Kiselyov@pitt.edu
authors.forename: Kirill
authors.initials: K
authors.lastname: Kiselyov
authors.forename: Grace A
authors.initials: GA
authors.lastname: Colletti
authors.forename: Austen
authors.initials: A
authors.lastname: Terwilliger
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ketchum
authors.forename: Christopher W P
authors.initials: CW
authors.lastname: Lyons
authors.forename: James
authors.initials: J
authors.lastname: Quinn
authors.forename: Shmuel
authors.initials: S
authors.lastname: Muallem
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D006801:Humans; D007501:Iron / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D009081:Mucolipidoses / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050051:Transient Receptor Potential Channels; D015032:Zinc / Q000378:metabolism
chemical_list: C416674:MCOLN1 protein, human; D008670:Metals; D050053:TRPM Cation Channels; D050051:Transient Receptor Potential Channels; D007501:Iron; D015032:Zinc; D002118:Calcium