The Role of Mitochondrial Calcium Signaling in the Pathophysiology of Cancer Cells

The pioneering work of Richard Altman on the presence of mitochondria in cells set in motion a field of research dedicated to uncovering the secrets of the mitochondria. Despite limitations in studying the structure and function of the mitochondria, advances in our understanding of this organelle prompted the development of potential treatments for various diseases, from neurodegenerative conditions to muscular dystrophy and cancer. As the powerhouses of the cell, the mitochondria represent the essence of cellular life and as such, a selective advantage for cancer cells. Much of the function of the mitochondria relies on Ca²⁺ homeostasis and the presence of effective Ca²⁺ signaling to maintain the balance between mitochondrial function and dysfunction and subsequently, cell survival. Ca²⁺ regulates the mitochondrial respiration rate which in turn increases ATP synthesis, but too much Ca²⁺ can also trigger the mitochondrial apoptosis pathway; however, cancer cells have evolved mechanisms to modulate mitochondrial Ca²⁺ influx and efflux in order to sustain their metabolic demand and ensure their survival. Therefore, targeting the mitochondrial Ca²⁺ signaling involved in the bioenergetic and apoptotic pathways could serve as potential approaches to treat cancer patients. This chapter will review the role of Ca²⁺ signaling in mediating the function of the mitochondria and its involvement in health and disease with special focus on the pathophysiology of cancer.