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Rapid CommunicationMinireview—A Latin American Perspective on Ion Channels

Modulation of Autophagy by Calcium Signalosome in Human Disease

Eduardo Cremonese Filippi-Chiela, Michelle S. Viegas, Marcos Paulo Thomé, Andreia Buffon, Marcia R. Wink and Guido Lenz
Molecular Pharmacology September 2016, 90 (3) 371-384; DOI: https://doi.org/10.1124/mol.116.105171
Eduardo Cremonese Filippi-Chiela
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
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Michelle S. Viegas
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
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Marcos Paulo Thomé
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
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Andreia Buffon
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
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Marcia R. Wink
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
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Guido Lenz
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
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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 Ca2+ 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 Ca2+ availability, coupled with a controlled ionic flow among the extracellular milieu, storage compartments, and the cytosol, is critical in determining the role played by Ca2+ on autophagy and on cell fate. The crosstalk between Ca2+ 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 Ca2+-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 Ca2+-mediated autophagy.

Footnotes

    • Received May 4, 2016.
    • Accepted July 18, 2016.
  • E.C.F.C. and M.S.V. contributed equally to this work.

  • This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Universal (Grants 475882/2012-1 and 458139/2014-9) and Novas Terapias Portadoras de Futuro (Grant 457394/2013-7); PROBITEC-CAPES (Grant 004/2012) and ICGEB BRA11/01. E.C.F.C., M.S.V., and M.P.T. are or were recipients of CNPq fellowships, and E.C.F.C. is a recipient of CAPES fellowship. M.R.W. and G.L. are recipients of research fellowships from CNPq.

  • dx.doi.org/10.1124/mol.116.105171.

  • Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 90 (3)
Molecular Pharmacology
Vol. 90, Issue 3
1 Sep 2016
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Rapid CommunicationMinireview—A Latin American Perspective on Ion Channels

Autophagy and Ca2+ in Human Disease

Eduardo Cremonese Filippi-Chiela, Michelle S. Viegas, Marcos Paulo Thomé, Andreia Buffon, Marcia R. Wink and Guido Lenz
Molecular Pharmacology September 1, 2016, 90 (3) 371-384; DOI: https://doi.org/10.1124/mol.116.105171

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Rapid CommunicationMinireview—A Latin American Perspective on Ion Channels

Autophagy and Ca2+ in Human Disease

Eduardo Cremonese Filippi-Chiela, Michelle S. Viegas, Marcos Paulo Thomé, Andreia Buffon, Marcia R. Wink and Guido Lenz
Molecular Pharmacology September 1, 2016, 90 (3) 371-384; DOI: https://doi.org/10.1124/mol.116.105171
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