Calcium Overload and Mitochondrial Metabolism

Abstract

Mitochondria calcium is a double-edged sword. While low levels of calcium are essential to maintain optimal rates of ATP production, extreme levels of calcium overcoming the mitochondrial calcium retention capacity leads to loss of mitochondrial function. In moderate amounts, however, ATP synthesis rates are inhibited in a calcium-titratable manner. While the consequences of extreme calcium overload are well-known, the effects on mitochondrial function in the moderately loaded range remain enigmatic. These observations are associated with changes in the mitochondria ultrastructure and cristae network. The present mini review/perspective follows up on previous studies using well-established cryo–electron microscopy and poses an explanation for the observable depressed ATP synthesis rates in mitochondria during calcium-overloaded states. The results presented herein suggest that the inhibition of oxidative phosphorylation is not caused by a direct decoupling of energy metabolism via the opening of a calcium-sensitive, proteinaceous pore but rather a separate but related calcium-dependent phenomenon. Such inhibition during calcium-overloaded states points towards mitochondrial ultrastructural modifications, enzyme activity changes, or an interplay between both events.

Protective Effect of Vitamin K2 (MK-7) on Acute Lung Injury Induced by Lipopolysaccharide in Mice

“…The calcium in mitochondria is a double-edged sword. Although low levels of calcium are crucial for maintaining most excellent ATP production speed rates, overcoming the extreme levels of mitochondrial calcium retention can lead to mitochondrial dysfunction [ 55 ]. So far, few studies have reported on the effects of VK2 on calcium homeostasis regulation.…”

ER stress promotes mitochondrial calcium overload and activates the ROS/NLRP3 axis to mediate fatty liver ischemic injury

“…Dysfunction of the calcium balance system under stress causes its disordered distribution and overload, leading to functional abnormalities. 41 Mitochondrial calcium overload can promote mROS production, leading to the opening of the mitochondrial permeability transition pore, release of cytochrome C, and apoptosis. 42 Multiple studies have reported the important role of ER-mitochondria Ca2+ signals in regulating cell death in various animal models.…”

Tumor Microenvironment-Sensitive Ca2+ Nanomodulator Combined with the Sonodynamic Process for Enhanced Cancer Therapy

“…4 Excessive accumulation of free Ca 2+ in the cytoplasm, referred to as "calcium overload", may cause mitochondrial dysfunction and cell death. 5 Overloaded Ca 2+ disrupts mitochondrial calcium homeostasis, upregulates caspase 3, and induces cell apoptosis. It is important to note that cancer cells are more susceptible to Ca 2+ overload than normal cells.…”

“…Ca 2+ is the second messenger in cells and has a significant impact on cell proliferation, apoptosis, migration, and gene expression . Excessive accumulation of free Ca 2+ in the cytoplasm, referred to as “calcium overload”, may cause mitochondrial dysfunction and cell death . Overloaded Ca 2+ disrupts mitochondrial calcium homeostasis, upregulates caspase 3, and induces cell apoptosis.…”