Interrelation between ROS and Ca2+ in aging and age-related diseases

Abstract

Calcium (Ca 2+ ) and reactive oxygen species (ROS) are versatile signaling molecules coordinating physiological and pathophysiological processes. While channels and pumps shuttle Ca 2+ ions between extracellular space, cytosol and cellular compartments, short-lived and highly reactive ROS are constantly generated by various production sites within the cell. Ca 2+ controls membrane potential, modulates mitochondrial adenosine triphosphate (ATP) production and affects proteins like calcineurin (CaN) or calmodulin (CaM), which, in turn, have a wide area of action. Overwhelming Ca 2+ levels within mitochondria efficiently induce and trigger cell death. In contrast, ROS comprise a diverse group of relatively unstable molecules with an odd number of electrons that abstract electrons from other molecules to gain stability. Depending on the type and produced amount, ROS act either as signaling molecules by affecting target proteins or as harmful oxidative stressors by damaging cellular components. Due to their wide range of actions, it is little wonder that Ca 2+ and ROS signaling pathways overlap and impact one another. Growing evidence suggests a crucial implication of this mutual interplay on the development and enhancement of age-related disorders, including cardiovascular and neurodegenerative diseases as well as cancer.

Melatonin to Rescue the Aged Heart: Antiarrhythmic and Antioxidant Benefits

“…In the aged myocardium, mitochondrial function is impaired at various levels including ROS formation, dynamics, and metabolism. Together with ROS, which is considered to be one of the primary determinants of aging [93][94][95], the superoxide anion, the hydroxyl radical, and hydrogen peroxide are in fact crucial molecules with important roles in cardiac physiology and pathophysiology through various signaling pathways [96].…”

Relationship Between Mitochondrial Structure and Bioenergetics in Pseudoxanthoma elasticum Dermal Fibroblasts

“…Besides the role of damaging and stressor agents, ROS can regulate both physiological and pathophysiological processes frequently overlapping calcium (Ca 2+ )-mediated signaling pathways controlling membrane potential and mitochondrial ATP production (Madreiter-Sokolowski et al, 2020). Free mitochondrial calcium was evaluated by loading control and PXE fibroblasts (Figures 5A,B) with Rhod-2 AM.…”

Opa1 relies on cristae preservation and ATP synthase to curtail reactive oxygen species accumulation in mitochondria

“…This configuration sustains mitochondrial ATP levels and homeostasis during starvation [ 31 ], limited respiratory substrate availability [ 30 ] or compromised electron transfer [ 29 ]. In this latter condition, improved bioenergetics and electron transfer by RCS may prevent both reactive oxygen species (ROS) generation [ 18 , 19 , [32] , [33] , [34] ], and their effects [ [35] , [36] , [37] , [38] ]. However, the role of mitochondrial ultrastructure in controlling ROS levels remains unclear [ 39 ].…”