Mitochondrial cristae remodeling in ischemic stroke: mechanisms and therapeutic perspectives

Mitochondrial cristae arrange the respiratory machinery within the inner membrane and change as ischemia gives way to reperfusion. Their organization depends on mitochondrial contact site and cristae organizing system assemblies, optic atrophy 1, adenosine triphosphate synthase, and cardiolipin. Disruption of these systems can impair energy production, facilitate neuronal death, and expose mitochondrial DNA to inflammatory sensors. This review brings structural work together with experimental stroke studies to examine how crista remodeling contributes to injury and recovery. Genetic manipulation of selected regulators has preserved mitochondrial structure and reduced injury in neurons and microglia. Most of these interventions preceded ischemia, leaving the speed and feasibility of repair after stroke onset uncertain. Pharmacological modulation and mitochondrial delivery offer ways to address this gap, particularly around reperfusion. Emerging strategies combine modulation of crista protein assemblies with cardiolipin directed treatment, mitochondrial antioxidant nanomedicine, organelle delivery, and control of local drug exposure. Their therapeutic evaluation can be aligned with distinct opportunities at reperfusion and during subsequent tissue recovery. Progress toward treatment will require evidence that a candidate reaches the affected brain cells, modifies the intended membrane assembly, and produces lasting neurological benefit. The available studies place crista remodeling within neuroprotective pathways and identify the experimental steps needed to evaluate it as a therapeutic target.