title: Modulation of Autophagy by Calcium Signalosome in Human Disease.
abstract: Autophagy is a catabolic process that is largely regulated by extracellular and intracellular signaling pathways that are central to cellular metabolism and growth. Mounting evidence has shown that ion channels and transporters are important for basal autophagy functioning and influence autophagy to handle stressful situations. Besides its role in cell proliferation and apoptosis, intracellular Ca(2+) is widely recognized as a key regulator of autophagy, acting through the modulation of pathways such as the mechanistic target of rapamycin complex 1, calcium/calmodulin-dependent protein kinase kinase 2, and protein kinase C. Proper spatiotemporal Ca(2+) availability, coupled with a controlled ionic flow among the extracellular milieu, storage compartments, and the cytosol, is critical in determining the role played by Ca(2+) on autophagy and on cell fate. The crosstalk between Ca(2+) and autophagy has a central role in cellular homeostasis and survival during several physiologic and pathologic conditions. Here we review the main findings concerning the mechanisms and roles of Ca(2+)-modulated autophagy, focusing on human disorders ranging from cancer to neurologic diseases and immunity. By identifying mechanisms, players, and pathways that either induce or suppress autophagy, new promising approaches for preventing and treating human disorders emerge, including those based on the modulation of Ca(2+)-mediated autophagy.
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil.
authors.forename: Eduardo Cremonese
authors.initials: EC
authors.lastname: Filippi-Chiela
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil.
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Viegas
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil.
authors.forename: Marcos Paulo
authors.initials: MP
authors.lastname: Thomé
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil.
authors.forename: Andreia
authors.initials: A
authors.lastname: Buffon
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil.
authors.forename: Marcia R
authors.initials: MR
authors.lastname: Wink
authors.affiliation: Graduate Program in Hepatology and Gastroenterology, Faculty of Medicine (E.C.F.-C.), and Gene Therapy Center (M.S.V.), Hospital de Clínicas de Porto Alegre; Department of Biophysics and Center of Biotechnology (M.P.T., G.L.) and Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy (M.R.W.), Federal University of Rio Grande do Sul (UFRGS); and Department of Health Sciences and Cell Biology Laboratory, Federal University of Health Sciences of Porto Alegre (A.B.), Porto Allegre, Brazil lenz@ufrgs.br.
authors.forename: Guido
authors.initials: G
authors.lastname: Lenz
mesh_terms: D001343:Autophagy; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002490:Central Nervous System / Q000378:metabolism; D004194:Disease; D006801:Humans; D008954:Models, Biological
chemical_list: D002118:Calcium