New Insights into the Mechanisms of Mitochondrial Preconditioning-Triggered Neuroprotection

Sonia      C. Correia; Susana      Cardoso; Renato      X. Santos; Cristina      Carvalho; Maria      S. Santos; George      Perry; Mark      A. Smith; Paula      I. Moreira

doi:10.2174/138161211798072490

Abstract

Mitochondria fulfill a number of essential cellular functions, being recognized that the strict regulation of the structure, function and turnover of these organelles is an immutable control node for the maintenance of neuronal integrity and homeostasis. Many lines of evidence posit that mitochondria constitute a convergence point of preconditioning - a paradigm that affords robust brain tolerance in the face of neurodegenerative insults. Indeed, it has been described that preconditioning activates an adaptive reprogramming of mitochondrial biology in response to a noxious stress-stimulus, which in turn will contribute to augment both mitochondrial and neuronal tolerance. Mitochondrial reactive species (ROS), mitochondrial ATP-sensitive potassium (mitoKATP) channels and mitochondrial permeability transition pore have been identified as specific mitochondrial mediators and targets of the adaptive program underlying preconditioning. Recent studies further link mitochondrial biogenesis, dynamics and mitophagy to preconditioning, thereby representing novel mechanisms by which preconditioning may mediate brain tolerance. The present review summarizes the current views on how mitochondrial biology is linked to preconditioning-induced neuroprotection. A better understanding of the mitochondrial mechanisms underlying preconditioning will help in the development of novel therapeutic approaches with the primary goal of modulating mitochondria to enhance brain tolerance against neurodegenerative events.

Keywords: Mitochondria, mitochondrial dynamics, mitochondria turnover, neuroprotection, preconditioning, reactive oxygen species, neurons, diazoxide, cytochrome c, mitophagy