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

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.

Exploration of the inhibition action of TPGS on tumor cells and its combined use with chemotherapy drugs

“…As shown ( Figure 2A, B ), significantly increased intracellular Ca 2+ levels were observed in MCF-7-ADR cells when compared with controls, and positively correlated with TPGS concentrations. As a key intracellular regulator, Ca 2+ concentration changes are closely related to cellular homeostasis (L. Zhang et al., 2022 ). When intracellular Ca 2+ concentrations increase in the cytoplasm, Ca 2+ intake by the mitochondria is reinforced, so we hypothesized that TPGS causes mitochondrial damage by increasing Ca 2+ concentrations.…”

Management of hypocalcaemia in the critically ill

“…Extrinsic stressors or cell stimuli, such as membrane depolarisation or extracellular signalling molecules, may temporarily increase cytoplasmic calcium by influx from extracellular or release from intracellular stores to interact with intracellular proteins [5,8]. During a transient increase in cytoplasmatic calcium, mitochondria utilize calcium as a signal for energy demand by activating adenosine triphosphate synthase and stimulating the electron transport chain to regulate reactive oxygen species production [8][9][10][11]. However, severe extrinsic stressors, such as cell damage, oxidative stress or inflammation, will cause excessive cytosolic calcium, which will be buffered in the cell's mitochondria [8,10].…”

Pro-Apoptotic Activity of Bioactive Compounds from Seaweeds: Promising Sources for Developing Novel Anticancer Drugs

“…In addition, laminarin induced apoptosis through ROS generation, endoplasmic reticulum (ER) stress, and DNA fragmentation [ 72 ]. The ER is considered a store of Ca 2+ , and an alteration in the level of Ca 2+ in the ER induces ER stress, which can activate the caspase -12 located in the ER, promoting apoptosis in a way independent of the mitochondria [ 120 , 121 ]. It is essential to underline that intrinsic apoptosis is associated with mitochondrial calcium concentration overload, where such excess can affect the release of pro-apoptotic factors by mitochondrial destruction [ 72 ].…”