Mitochondrial Ca2+ Homeostasis: Emerging Roles and Clinical Significance in Cardiac Remodeling

Abstract

Mitochondria are the sites of oxidative metabolism in eukaryotes where the metabolites of sugars, fats, and amino acids are oxidized to harvest energy. Notably, mitochondria store Ca2+ and work in synergy with organelles such as the endoplasmic reticulum and extracellular matrix to control the dynamic balance of Ca2+ concentration in cells. Mitochondria are the vital organelles in heart tissue. Mitochondrial Ca2+ homeostasis is particularly important for maintaining the physiological and pathological mechanisms of the heart. Mitochondrial Ca2+ homeostasis plays a key role in the regulation of cardiac energy metabolism, mechanisms of death, oxygen free radical production, and autophagy. The imbalance of mitochondrial Ca2+ balance is closely associated with cardiac remodeling. The mitochondrial Ca2+ uniporter (mtCU) protein complex is responsible for the uptake and release of mitochondrial Ca2+ and regulation of Ca2+ homeostasis in mitochondria and consequently, in cells. This review summarizes the mechanisms of mitochondrial Ca2+ homeostasis in physiological and pathological cardiac remodeling and the regulatory effects of the mitochondrial calcium regulatory complex on cardiac energy metabolism, cell death, and autophagy, and also provides the theoretical basis for mitochondrial Ca2+ as a novel target for the treatment of cardiovascular diseases.

The adhesion G-protein coupled receptor VLGR1/ADGRV1 controls autophagy

“…The absence of VLGR1 resulted in a disturbance in the MAM architecture and the dysregulation of the Ca 2+ transient from ER to mitochondria 15 . The disruption of Ca 2+ signalling between the ER and mitochondria and the resulting imbalance of Ca 2+ homeostasis induces mitophagy 38,39 , a specific form of autophagy which selectively removes defective mitochondria 22 . We additionally identified several proteins related to mitophagy, as potential interactors of VLGR1 (see Figure 1E, H) supporting the association of VLGR1 with this form of autophagy.…”

The adhesion G protein‐coupled receptor VLGR1/ADGRV1 controls autophagy

“…17 The absence of VLGR1 resulted in a disturbance in the MAM architecture and the dysregulation of the Ca 2+ transient from ER to mitochondria. 16 The disruption of Ca 2+ signalling between the ER and mitochondria and the resulting imbalance of Ca 2+ homeostasis induces mitophagy, 82,83 a specific form of autophagy which selectively removes defective mitochondria. 23 We additionally identified several proteins related to mitophagy, as potential interactors of VLGR1 (see Figure 2C,F), supporting the association of VLGR1 with this form of autophagy.…”

Bioelectricity: A top-down control model to promote more effective aging interventions

“…Reduced mitochondrial membrane potential impairs the uptake and release of calcium by the mitochondria, leading to dysregulated calcium homeostasis [27]. This can subsequently affect various calcium-dependent processes, including cellular proliferation, apoptosis, and autophagy, all of which have been implicated in the aging process [28].…”