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

Int J Mol Sci. 2022 Jun 15;23(12):6667. doi: 10.3390/ijms23126667.

Abstract

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.

Keywords: MCU; calcium homeostasis; calcium regulation; mitochondrial calcium; tumor.

Publication types

  • Review

MeSH terms

  • Calcium Channels* / metabolism
  • Calcium* / metabolism
  • Calcium, Dietary
  • Cytoplasm / metabolism
  • Mitochondria / metabolism

Substances

  • Calcium Channels
  • Calcium, Dietary
  • mitochondrial calcium uniporter
  • Calcium