Mitophagy, a potential therapeutic target for stroke

Abstract

Mitochondria autophagy, termed as mitophagy, is a mechanism of specific autophagic elimination of mitochondria. Mitophagy controls the quality and the number of mitochondria, eliminating dysfunctional or excessive mitochondria that can generate reactive oxygen species (ROS) and cause cell death. Mitochondria are centrally implicated in neuron and tissue injury after stroke, due to the function of supplying adenosine triphosphate (ATP) to the tissue, regulating oxidative metabolism during the pathologic process, and contribution to apoptotic cell death after stroke. As a catabolic mechanism, mitophagy links numbers of a complex network of mitochondria, and affects mitochondrial dynamic process, fusion and fission, reducing mitochondrial production of ROS, mediated by the mitochondrial permeability transition pore (MPTP). The precise nature of mitophagy’s involvement in stroke, and its underlying molecular mechanisms, have yet to be fully clarified. This review aims to provide a comprehensive overview of the integration of mitochondria with mitophagy, also to introduce and discuss recent advances in the understanding of the potential role, and possible signaling pathway, of mitophagy in the pathological processes of both hemorrhagic and ischemic stroke. The author also provides evidence to explain the dual role of mitophagy in stroke.

Gene Expression Dynamics at the Neurovascular Unit During Early Regeneration After Cerebral Ischemia/Reperfusion Injury in Mice

“…Late induction of PINK1, a mitophagy regulator to clear damaged mitochondria, indicates potential resolution of mitochondrial dysfunction and repair of I/R injury as shown previously in cardiac and renal ischemia (Siddall et al, 2013;Tang et al, 2018). The role of mitophagy in ischemic stroke is however not fully understood (Guan et al, 2018).…”

WITHDRAWN: Combination of Paeoniflorin and Calycosin-7-glucoside Promotes Ischemic Stroke Recovery via the PI3K/AKT Signaling Pathway

“…Ischemia and hypoxia cause changes in the volume of adenosine triphosphate (ATP) in brain tissue 3 , and K + , Ca 2+ and Na + ions in the cells are dysregulated 4,5 . The intracellular pH changes, causing anaerobic metabolism of glucose in the cells to produce lactic acid.…”

The Effect of Acupuncture for ATP Activity in Brain Diseases: Protocol of a Systematic Review and Meta-Analysis of Animal Experiments

“…Once ATP depletion occurs, cell damage in brain can lead to cell death due to necrosis or apoptosis [8,9]. Guan [10] and Zhen [11] et al both pointed out that the decrease of ATP and lacking of nutrient and oxygen are the main cause of cell death and tissue infarction after ischemic stroke.…”