Abstract
Mitochondria actively participate in the regulation of cell respiratory mechanisms, metabolic processes, and energy homeostasis in the central nervous system (CNS). Because of the requirement of high energy, neuronal functionality and viability are largely dependent on mitochondrial functionality. In the context of CNS disorders, disruptions of metabolic homeostasis caused by mitochondrial dysfunction lead to neuronal cell death and neuroinflammation. Therefore, restoring mitochondrial function becomes a primary therapeutic target. Recently, accumulating evidence suggests that active mitochondria are secreted into the extracellular fluid and potentially act as non-cell-autonomous signals in CNS pathophysiology. In this mini-review, we overview findings that implicate the presence of cell-free extracellular mitochondria and the critical role of intercellular mitochondrial transfer in various rodent models of CNS disorders. We also discuss isolated mitochondrial allograft as a novel therapeutic intervention for CNS disorders.
Highlights
Mitochondria are the powerhouse of cells and essential for maintaining cellular function in mammals (Devine and Kittler, 2018)
When astrocytic CD38 was stimulated by NAD+, O-GlcNAc posttranslational modification in mitochondrial proteins was amplified, and these O-GlcNAcylated mitochondria maintained mitochondrial DNA (mtDNA) content and membrane potential in extracellular space, improving neuroprotective effects after mitochondrial transfer (Park et al, 2020b)
In the context of Parkinson’s disease (PD), the mechanism of transmitophagy may be crucial to maintain mitochondrial function in dopaminergic neurons and prevent neuroinflammation mediated by disrupted mitochondrial secretion (Morales et al, 2020)
Summary
Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States. Mitochondria actively participate in the regulation of cell respiratory mechanisms, metabolic processes, and energy homeostasis in the central nervous system (CNS). In the context of CNS disorders, disruptions of metabolic homeostasis caused by mitochondrial dysfunction lead to neuronal cell death and neuroinflammation. Accumulating evidence suggests that active mitochondria are secreted into the extracellular fluid and potentially act as non-cell-autonomous signals in CNS pathophysiology. In this mini-review, we overview findings that implicate the presence of cell-free extracellular mitochondria and the critical role of intercellular mitochondrial transfer in various rodent models of CNS disorders.
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