Role of mitochondrial Ca2+ in stroke: From molecular mechanism to treatment strategy (Review)
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- Published online on: July 28, 2025 https://doi.org/10.3892/mmr.2025.13636
- Article Number: 271
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Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Abstract
Mitochondria serve a pivotal role in the pathological mechanisms of stroke, particularly in the regulation of intracellular calcium homeostasis. Stroke‑induced ischemia and reperfusion injury frequently result in disruptions of mitochondrial calcium ion (Ca2+) transport, characterized by Ca2+ overload. This imbalance directly impairs mitochondrial function and triggers neuronal death. Mitochondrial Ca2+ transport involves calcium influx, primarily mediated by the mitochondrial calcium uniporter (MCU) complex, and efflux, primarily through the sodium‑calcium exchanger (NCLX), making this mechanism a critical therapeutic target in stroke. The present review systematically explores the central role of mitochondrial Ca2+ transport in ischemia/reperfusion injury, with an in‑depth analysis of its pathological mechanisms in cellular energy metabolism, oxidative stress and apoptotic signaling pathways. Additionally, this review summarizes recent advancements in therapeutic strategies targeting mitochondrial Ca2+ transport, including MCU inhibitors, NCLX activators, antioxidant therapies and combination treatments. It also highlights the potential of Ca2+ signaling for early stroke diagnosis and reviews progress in dynamic monitoring technologies for mitochondrial Ca2+, such as fluorescence probes and super‑resolution microscopy. Despite significant progress in basic research, challenges remain in translating these findings into clinical applications. Future efforts should focus on elucidating the regulatory mechanisms of mitochondrial Ca2+, developing diagnostic tools and optimizing therapeutic interventions to improve stroke prognosis and enhance the quality of life of patients.
