Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease.

Abstract

In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity and activity. In damaged or diseased brains, mitochondrial dysfunction reduces adenosine triphosphate (ATP) levels and impairs ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial capacity to generate ATP may be fundamental in restoring neuronal function. Recent studies in animals and humans have demonstrated that endogenous mitochondria may be released into the extracellular environment and transported or exchanged between cells in the CNS. Under pathological conditions in the CNS, intercellular mitochondria transfer contributes to new classes of signaling and multifunctional cellular activities, thereby triggering deleterious effects or promoting beneficial responses. Therefore, to take full advantage of the beneficial effects of mitochondria, it may be useful to transplant healthy and viable mitochondria into damaged tissues. In this review, we describe recent findings on the mechanisms of mitochondria transfer and provide an overview of experimental methodologies, including tissue sourcing, mitochondrial isolation, storage, and modification, aimed at optimizing mitochondria transplantation therapy for CNS disorders. Additionally, we examine the clinical relevance and potential strategies for the therapeutic application of mitochondria transplantation.