Mitochondrial dysfunction in cerebrovascular diseases

Mitochondria are central regulators of cerebrovascular health through their control of energy metabolism, Ca2+ homeostasis, and redox signaling, and their dysfunction represents a convergent pathogenic mechanism across cerebrovascular diseases. In ischemic stroke, mitochondrial failure exacerbates neuronal injury via permeability transition pore opening, oxidative stress, and bioenergetic collapse, while altered mitochondrial dynamics and the release of mitochondrial damage-associated molecular patterns amplify neuroinflammation during reperfusion. Beyond stroke, mitochondrial dysfunction contributes to intracranial aneurysms, atherosclerotic stenosis, and vascular malformations, where oxidative stress, mitochondrial DNA instability, and cell type-specific metabolic reprogramming drive vascular remodeling and lesion progression. In this review, we integrate recent evidence highlighting context- and stage-dependent roles of mitochondria in cerebrovascular pathology and discuss implications for biomarker discovery, therapeutic targeting, and translational strategies.