RT Journal Article
SR Electronic
T1 Modulation of Autophagy by Calcium Signalosome in Human Disease
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 371
OP 384
DO 10.1124/mol.116.105171
VO 90
IS 3
A1 Eduardo Cremonese Filippi-Chiela
A1 Michelle S. Viegas
A1 Marcos Paulo Thomé
A1 Andreia Buffon
A1 Marcia R. Wink
A1 Guido Lenz
YR 2016
UL http://molpharm.aspetjournals.org/content/90/3/371.abstract
AB 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.