EXPRESS: Intercellular Mitochondrial Transfer in Ischemic Stroke: Emerging Roles of Microglia

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• Mitochondrial dysfunction is a key factor in cerebral ischemia-reperfusion injury, impacting energy, oxidative stress, and inflammation.
• Intercellular mitochondrial transfer is a potential adaptive mechanism for brain metabolic support post-injury.

Purpose of the Study:

• To review proposed pathways of intercellular mitochondrial transfer in the injured brain.
• To differentiate the roles of astrocyte- and microglia-mediated transfer.
• To examine the influence of mitochondrial components and damage-associated molecular patterns (DAMPs) on post-ischemic inflammation.

Main Methods:

• Literature review of proposed intercellular mitochondrial transfer mechanisms.
• Analysis of astrocyte-to-neuron and microglia-mediated transfer pathways.
• Examination of mitochondrial components (mtDNA, cardiolipin, cytochrome c) and their immune signaling roles.

Main Results:

• Three primary transfer pathways are discussed: tunneling nanotubes (TNTs) for intact mitochondria, extracellular vesicles (EVs) for mitochondrial components, and gap junctions.
• TNT-mediated transfer is linked to bioenergetic rescue, while EV-mediated transfer influences intercellular signaling.
• Mitochondrial DAMPs activate innate immunity, exacerbating post-ischemic inflammation.

Conclusions:

• Intercellular mitochondrial transfer, via TNTs and EVs, plays a complex role in cerebral ischemia-reperfusion.
• The functional outcomes depend on donor cell status, cargo integrity, and disease progression.
• Understanding these mechanisms is crucial for developing therapeutic strategies targeting brain injury.