Mitochondrial Dynamics in Cerebral Ischemia-Reperfusion Injury

Cerebral ischaemia followed by reperfusion triggers a cascade of events centred on mitochondrial dynamics, comprising fission, fusion and selective autophagic removal of damaged organelles. In the acute phase of ischaemia, energy deprivation and calcium overload provoke excessive mitochondrial fragmentation, predominately driven by dynamin-related protein 1 (Drp1) activation. This fragmentation impairs ATP synthesis and augments generation of reactive oxygen species (ROS), fuelling neuronal death pathways and neuroinflammation. Upon reperfusion, restoration of blood flow exacerbates oxidative stress, further destabilising mitochondrial membranes and opening the mitochondrial permeability transition pore (mPTP). Counterbalancing mechanisms engage fusion proteins such as mitofusins and optic atrophy 1 (OPA1) to restore network integrity, while mitophagy systems clear irreversibly damaged mitochondria. However, imbalance between fission and fusion exacerbates calcium dysregulation and cytokine release by microglia, amplifying secondary injury. Advances in understanding the interplay between mitochondrial quality control and inflammatory signalling have highlighted novel therapeutic targets to preserve neuronal viability and extend the window for neuroprotection in stroke.

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Mitochondrial Dynamics in Cerebral Ischemia-Reperfusion Injury publication trend

The graph below shows the total number of articles in mitochondrial dynamics in cerebral ischemia-reperfusion injury across all publications each year (not limited to Nature Index journals).

Technical terms

Mitochondrial fission: Division of a single mitochondrion into two or more organelles, largely mediated by Drp1, which influences energy production and apoptosis.

Mitochondrial fusion: Coalescence of separate mitochondria into a reticular network, regulated by mitofusins and OPA1, to maintain respiratory efficiency and DNA integrity.

Mitophagy: Selective autophagic clearance of dysfunctional or supernumerary mitochondria, critical for cellular homeostasis and prevention of oxidative stress.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen, generated by the electron transport chain, which can damage proteins, lipids and DNA when in excess.

Mitochondrial permeability transition pore (mPTP): A non-specific channel that opens under pathological conditions, dissipating membrane potential and triggering cell death pathways.

References

1. Mitochondrial stress: a key role of neuroinflammation in stroke. Journal of Neuroinflammation (2024).
2. New TIPARP inhibitor rescues mitochondrial function and brain injury in ischemic stroke. Pharmacological Research (2024).
3. E2F1/CDK5/DRP1 axis mediates microglial mitochondrial division and autophagy in the pathogenesis of cerebral ischemia‐reperfusion injury. Clinical and Translational Medicine (2025).