Endoplasmic Reticulum-Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival.
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TLDR
The emerging role of ER–mitochondrial Ca2+ fluxes underlying these cancer-related features, including metastasis and invasion processes, are discussed, which seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics.Abstract:
Calcium ions (Ca2+) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via “mitochondria-associated ER membranes” (MAMs) where ER-mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER-mitochondrial Ca2+ fluxes for their survival since they drive the TCA cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter (MCU) and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α (HIF1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER-mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER-mitochondrial Ca2+ fluxes underlying these cancer-related features.read more
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Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death.
Saverio Marchi,Simone Patergnani,Sonia Missiroli,Giampaolo Morciano,Alessandro Rimessi,Mariusz R. Wieckowski,Carlotta Giorgi,Paolo Pinton +7 more
TL;DR: The different molecular players involved in the transfer of Ca2+ ions from the ER lumen to the mitochondrial matrix are described and how modifications in both ER-mitochondria contact sites andCa2+ signaling can alter the cell death execution program are described.
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The regulation of autophagy by calcium signals: Do we have a consensus?
TL;DR: The sequestration of Ca2+ by mitochondria during physiological signalling appears necessary to maintain cellular bio-energetics, thereby suppressing AMPK-dependent autophagy.
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Calcium signaling and cell cycle: Progression or death.
Juliette Humeau,José Manuel Bravo-San Pedro,Ilio Vitale,Lucía Núñez,Carlos Villalobos,Guido Kroemer,Laura Senovilla +6 more
TL;DR: How Ca2+ participates in the exogenous and endogenous signals controlling cell proliferation, as well as in the mechanisms by which cells die if irreparable cell cycle damage occurs, is discussed.
Journal ArticleDOI
Emerging molecular mechanisms in chemotherapy: Ca 2+ signaling at the mitochondria-associated endoplasmic reticulum membranes.
Martijn Kerkhofs,Mart Bittremieux,Giampaolo Morciano,Carlotta Giorgi,Paolo Pinton,Jan B. Parys,Geert Bultynck +6 more
TL;DR: Recent studies that connect ER–mitochondrial Ca2+ transfer, tumor suppressors and oncogenes at the MAMs, and chemotherapy are discussed.
Journal ArticleDOI
Role of Mitochondria-Associated ER Membranes in Calcium Regulation in Cancer-Specific Settings
Giampaolo Morciano,Saverio Marchi,Claudia Morganti,Luigi Sbano,Mart Bittremieux,Martijn Kerkhofs,Mariangela Corricelli,Alberto Danese,Agnieszka Karkucinska-Wieckowska,Mariusz R. Wieckowski,Geert Bultynck,Carlotta Giorgi,Paolo Pinton +12 more
TL;DR: This review presents the current state of the art regarding MAM-resident proteins and their relevance, alterations, and deregulating functions in different types of cancer from a cell biology and clinical perspective.
References
More filters
Journal ArticleDOI
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Journal ArticleDOI
The metabolism of tumors in the body.
TL;DR: The question of whether tumor cells in living animals can be killed off through lack of energy, and the related question of how the tumors are supplied with oxygen and glucose in the body are discussed.
Journal ArticleDOI
An inhibitor of Bcl-2 family proteins induces regression of solid tumours
Tilman Oltersdorf,Steven W. Elmore,Alexander R. Shoemaker,Robert C. Armstrong,David J. Augeri,Barbara A. Belli,Milan Bruncko,Thomas L. Deckwerth,Jürgen Dinges,Philip J. Hajduk,Mary K. Joseph,Shinichi Kitada,Stanley J. Korsmeyer,Stanley J. Korsmeyer,Kunzer Aaron R,Anthony Letai,Chi Li,Michael J. Mitten,David G. Nettesheim,Shi Chung Ng,Paul Nimmer,Jacqueline M. O'Connor,Anatol Oleksijew,Andrew M. Petros,John C. Reed,Wang Shen,Stephen K. Tahir,Craig B. Thompson,Kevin J. Tomaselli,Baole Wang,Wendt Michael D,Haichao Zhang,Stephen W. Fesik,Saul H. Rosenberg +33 more
TL;DR: Mechanistic studies reveal that ABT-737 does not directly initiate the apoptotic process, but enhances the effects of death signals, displaying synergistic cytotoxicity with chemotherapeutics and radiation.
Journal ArticleDOI
The Warburg Effect: How Does it Benefit Cancer Cells?
TL;DR: Several proposed explanations for the function of Warburg Effect are analyzed, emphasize their rationale, and discuss their controversies.
Journal ArticleDOI
Aerobic Glycolysis: Meeting the Metabolic Requirements of Cell Proliferation
TL;DR: In this paper, the authors provide a detailed accounting of the biosynthetic requirements to construct a new cell and illustrate the importance of glycolysis in providing carbons to generate biomass.