title: Calcium regulates cell death in cancer: Roles of the mitochondria and mitochondria-associated membranes (MAMs).
abstract: Until 1972, the term 'apoptosis' was used to differentiate the programmed cell death that naturally occurs in organismal development from the acute tissue death referred to as necrosis. Many studies on cell death and programmed cell death have been published and most are, at least to some degree, related to cancer. Some key proteins and molecular pathways implicated in cell death have been analyzed, whereas others are still being actively researched; therefore, an increasing number of cellular compartments and organelles are being implicated in cell death and cancer. Here, we discuss the mitochondria and subdomains of the endoplasmic reticulum (ER) that interact with mitochondria, the mitochondria-associated membranes (MAMs), which have been identified as critical hubs in the regulation of cell death and tumor growth. MAMs-dependent calcium (Ca2+) release from the ER allows selective Ca2+uptake by the mitochondria. The perturbation of Ca2+homeostasis in cancer cells is correlated with sustained cell proliferation and the inhibition of cell death through the modulation of Ca2+signaling. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.
authors.affiliation: Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Danese
authors.affiliation: Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Patergnani
authors.affiliation: Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bonora
authors.affiliation: Dept. of Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Mariusz R
authors.initials: MR
authors.lastname: Wieckowski
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, Section of Human Anatomy and Histology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Previati
authors.affiliation: Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. Electronic address: carlotta.giorgi@unife.it.
authors.forename: Carlotta
authors.initials: C
authors.lastname: Giorgi
authors.affiliation: Dept. of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy. Electronic address: paolo.pinton@unife.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology; D016923:Cell Death; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000502:physiology; D009363:Neoplasm Proteins / Q000502:physiology; D015513:Oncogene Proteins / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015220:Calcium Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; C034703:mitochondrial calcium uniporter; D002118:Calcium
keywords: Apoptosis; Autophagy; Calcium (Ca(2+)); Endoplasmic reticulum; Mitochondria associated membranes (MAMs); Tumor