The two faces of mitochondrial Ca
Abstract
Mitochondrial Ca²⁺ dysregulation is a central pathogenic event in skeletal muscle disorders, yet the dichotomy between overload and deficiency is often overlooked. This review summarizes mechanisms governing mitochondrial Ca²⁺ transport and sarcoplasmic reticulum-mitochondria communication. We examine prerequisites of Ca²⁺ overload, including RyR1/SERCA dysfunction and mitochondrial calcium uniporter (MCU) complex remodeling, leading to suppressed ATP synthesis, reactive oxygen species overproduction, and necrosis. Conversely, we address mitochondrial Ca²⁺ deficiency in aging, sarcopenia, and diabetes, resulting from altered MCU stoichiometry and reduced organelle tethering, causing metabolic inflexibility and impaired antioxidant defense. Additionally, therapeutic strategies limiting Ca²⁺ overload and prospects of pharmacological MCU activation to enhance bioenergetics in sarcopenia are discussed.
The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.
Research summary
Mitochondrial calcium dysregulation, specifically the balance between overload and deficiency, is a fundamental mechanistic driver of cellular senescence and metabolic decline in aging. This review provides a solid mechanistic framework linking mitochondrial calcium handling to sarcopenia and metabolic inflexibility, offering potential targets for interventions that address root causes of aging rather than just symptoms.
Author of this paper? Send a correction.