Regulation of calcium fluxes by GPX8, a type-II transmembrane peroxidase enriched at the mitochondria-associated endoplasmic reticulum membrane
Autor: | Alessandro Rimessi, Tiziana Anelli, Paolo Pinton, Edgar Djaha Yoboue, Roberto Sitia |
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Přispěvatelé: | Yoboue, Edgar Djaha, Rimessi, Alessandro, Anelli, Tiziana, Pinton, Paolo, Sitia, Roberto |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Physiology Clinical Biochemistry Socio-culturale Biology Biochemistry 03 medical and health sciences Cytosol mitochondria associated membrane (MAM) membrane topology Protein Domains Calcium flux Humans glutathione peroxidase Molecular Biology General Environmental Science Endoplasmic reticulum membrane 030102 biochemistry & molecular biology Endoplasmic reticulum glutathione peroxidases Cell Membrane STIM1 Cell Biology calcium (Ca2+) signaling endoplasmic reticulum mitochondria associated membrane (MAM) calcium (Ca2+) signaling glutathione peroxidases membrane topology Transmembrane protein Cell biology Mitochondria stomatognathic diseases Transmembrane domain endoplasmic reticulum 030104 developmental biology Peroxidases Membrane topology General Earth and Planetary Sciences Calcium human activities HeLa Cells |
Popis: | Glutathione peroxidases (GPXs) are enzymes that are present in almost all organisms with the primary function of limiting peroxide accumulation. In mammals, two of the eight members (GPX7 and GPX8) reside in the endoplasmic reticulum (ER). A peculiar feature of GPX8 is the concomitant presence of a conserved N-terminal transmembrane domain (TMD) and a C-terminal KDEL-like motif for ER localization. Aims: Investigating whether and how GPX8 impacts Ca2+ homeostasis and signaling. Results: We show that GPX8 is enriched in mitochondria-associated membranes and regulates Ca2+ storage and fluxes. Its levels correlate with [Ca2+]ER, and cytosolic and mitochondrial Ca2+ fluxes. GPX7, which lacks a TMD, does not share these properties. Deleting or replacing the GPX8 TMD with an unrelated N-terminal membrane integration sequence abolishes all effects on Ca2+ fluxes, whereas appending the GPX8 TMD to GPX7 transfers the Ca2+-regulating properties. Innovation and Conclusion: The notion that the TMD of GPX8, i... |
Databáze: | OpenAIRE |
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