The Regulatory Roles of Mitochondrial Calcium and the Mitochondrial Calcium Uniporter in Tumor Cells

Mitochondria, as the main site of cellular energy metabolism and the generation of oxygen free radicals, are the key switch for mitochondria-mediated endogenous apoptosis. Ca²⁺ is not only an important messenger for cell proliferation, but it is also an indispensable signal for cell death. Ca²⁺ participates in and plays a crucial role in the energy metabolism, physiology, and pathology of mitochondria. Mitochondria control the uptake and release of Ca²⁺ through channels/transporters, such as the mitochondrial calcium uniporter (MCU), and influence the concentration of Ca²⁺ in both mitochondria and cytoplasm, thereby regulating cellular Ca²⁺ homeostasis. Mitochondrial Ca²⁺ transport-related processes are involved in important biological processes of tumor cells including proliferation, metabolism, and apoptosis. In particular, MCU and its regulatory proteins represent a new era in the study of MCU-mediated mitochondrial Ca²⁺ homeostasis in tumors. Through an in-depth analysis of the close correlation between mitochondrial Ca²⁺ and energy metabolism, autophagy, and apoptosis of tumor cells, we can provide a valuable reference for further understanding of how mitochondrial Ca²⁺ regulation helps diagnosis and therapy.