Calcium (Ca2+) is an incredibly versatile signaling ion that dictates cellular life and death. Many of these decisions are taken by the mitochondria, which are strategically positioned very close to the endoplasmic reticulum (ER), the main intracellular Ca2+ store. Thus, while spontaneous low-level Ca2+ release from the ER transfers to the mitochondria to support housekeeping bioenergetics, large and sustained Ca2+ signals generate mitochondrial Ca2+ overload inducing apoptosis. Therefore, cell fate critically relies on the transfer of Ca2+ from the ER to the mitochondria. This depends on the function of Ca2+-transport systems, including the inositol 1,4,5-trisphosphate receptors (InsP3R) and ryanodine receptor (RyR) Ca2+ release channels in the ER, the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane and the recently described components of the inner membrane mitochondrial Ca2 + uniporter (MCU) complex. The latter represents the dominant pathway for Ca2 + influx into the mitochondrial matrix and includes the Ca2+-transport unit MCU and its associated proteins MICU1/2, MCUR1 and EMRE. Clearly, altered Ca2+ dynamics and oncogenesis are tightly linked. Indeed, changes in the expression and regulation of Ca2+-transport systems directly impact several hall-marks of cancer cells. Moreover, a growing list of tumor suppressors and oncogenes have been elucidated to execute part of their functions through Ca2+ signaling, either impacting the expression of Ca2+ channels and pumps or directly regulating the Ca2+-flux properties of these transporters by forming multi-protein complexes. Finally, also successful anti-cancer therapies appear to rely on their ability to elicit intracellular Ca2+ responses. Yet, insights in the role of the ER-mitochondrial Ca2+ communication in cell metabolism, cell cycle and anti/apoptotic signals and how this aspect is altered in oncogenesis and cancer cells are just beginning to be revealed, although important discoveries in this area have been very recently made.
The aim of this Research Topic is to thoroughly review current knowledge on the ER-mitochondrial Ca2+ communication in cancer, and to discuss its potential as a therapeutic target. We welcome original contributions, short communications and review articles.
Calcium (Ca2+) is an incredibly versatile signaling ion that dictates cellular life and death. Many of these decisions are taken by the mitochondria, which are strategically positioned very close to the endoplasmic reticulum (ER), the main intracellular Ca2+ store. Thus, while spontaneous low-level Ca2+ release from the ER transfers to the mitochondria to support housekeeping bioenergetics, large and sustained Ca2+ signals generate mitochondrial Ca2+ overload inducing apoptosis. Therefore, cell fate critically relies on the transfer of Ca2+ from the ER to the mitochondria. This depends on the function of Ca2+-transport systems, including the inositol 1,4,5-trisphosphate receptors (InsP3R) and ryanodine receptor (RyR) Ca2+ release channels in the ER, the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane and the recently described components of the inner membrane mitochondrial Ca2 + uniporter (MCU) complex. The latter represents the dominant pathway for Ca2 + influx into the mitochondrial matrix and includes the Ca2+-transport unit MCU and its associated proteins MICU1/2, MCUR1 and EMRE. Clearly, altered Ca2+ dynamics and oncogenesis are tightly linked. Indeed, changes in the expression and regulation of Ca2+-transport systems directly impact several hall-marks of cancer cells. Moreover, a growing list of tumor suppressors and oncogenes have been elucidated to execute part of their functions through Ca2+ signaling, either impacting the expression of Ca2+ channels and pumps or directly regulating the Ca2+-flux properties of these transporters by forming multi-protein complexes. Finally, also successful anti-cancer therapies appear to rely on their ability to elicit intracellular Ca2+ responses. Yet, insights in the role of the ER-mitochondrial Ca2+ communication in cell metabolism, cell cycle and anti/apoptotic signals and how this aspect is altered in oncogenesis and cancer cells are just beginning to be revealed, although important discoveries in this area have been very recently made.
The aim of this Research Topic is to thoroughly review current knowledge on the ER-mitochondrial Ca2+ communication in cancer, and to discuss its potential as a therapeutic target. We welcome original contributions, short communications and review articles.
