Mitochondrial Quality Control and Disease: Insights into Ischemia-Reperfusion Injury

Abstract

Mitochondria are key regulators of cell fate during disease. They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C. Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network. Quality control mechanisms are largely regulated by mitochondrial dynamics and mitophagy. The processes of mitochondrial fission (division) and fusion allow for damaged mitochondria to be segregated and facilitate the equilibration of mitochondrial components such as DNA, proteins, and metabolites. The process of mitophagy are responsible for the degradation and recycling of damaged mitochondria. These mitochondrial quality control mechanisms have been well studied in chronic and acute pathologies such as Parkinson's disease, Alzheimer's disease, stroke, and acute myocardial infarction, but less is known about how these two processes interact and contribute to specific pathophysiologic states. To date, evidence for the role of mitochondrial quality control in acute and chronic disease is divergent and suggests that mitochondrial quality control processes can serve both survival and death functions depending on the disease state. This review aims to provide a synopsis of the molecular mechanisms involved in mitochondrial quality control, to summarize our current understanding of the complex role that mitochondrial quality control plays in the progression of acute vs chronic diseases and, finally, to speculate on the possibility that targeted manipulation of mitochondrial quality control mechanisms may be exploited for the rationale design of novel therapeutic interventions.

Baicalin protects H9c2 cardiomyocytes against hypoxia/reoxygenation‐induced apoptosis and oxidative stress through activation of mitochondrial aldehyde dehydrogenase 2

“…We know that the mitochondrial apoptosis pathway is the intrinsic pathway of apoptosis and involved in the development of many diseases . Increasing evidence has shown that I/R injury activates mitochondria‐mediated apoptosis as revealed as by the increased ratio of Bax/Bcl‐2 and the release of cytochrome c , leading to downstream caspase cascade . Further study showed that baicalin pretreatment inhibits mitochondrial damage‐mediated apoptosis leading to protecting against myocardial I/R injury .…”

“…39 Increasing evidence has shown that I/R injury activates mitochondriamediated apoptosis as revealed as by the increased ratio of Bax/Bcl-2 and the release of cytochrome c, leading to downstream caspase cascade. 40 Further study showed that baicalin pretreatment inhibits mitochondrial damage-mediated apoptosis leading to protecting against myocardial I/R injury. 21 Similarly, in current study, we found that pretreatment with baicalin obviously alleviated H/R-induced increased expression of cytochrome c, Bax (pro-apoptotic protein) and decreased expression of Bcl-2 (anti-apoptotic protein) in H9c2 cells.…”

Mitophagy imbalance in cardiomyocyte ischaemia/reperfusion injury

“…7 In mammalian cells, classic autophagy is clarified into three types: macroautophagy, microautophagy and chaperone-mediated autophagy. [7][8][9] The processes of macroautophagy and microautophagy need to form vesicles. In macroautophagy, vesicle formation occurs in the cytosol, which is a double-membrane structure known as autophagosome.…”

The role of 5‐hydroxymethylcytosine in mitochondria after ischemic stroke

“…Ischemic stroke leads to necrotic and apoptotic cell death due to hypoxia or anoxia in brain tissues. Although cerebral reperfusion is important for salvaging ischemic brain tissue, it also results in a loss of mitochondrial function and disrupts the dynamic balance of mitochondrial gene expression, thereby reducing ATP synthesis (Anzell, Maizy, Przyklenk, & Sanderson, 2017;Crack & Taylor, 2005;Pulsinelli & Duffy, 1983). Mitochondrial DNA encodes genes related to ATP synthesis, such as Complex I (ND1, ND2, ND3, ND4, ND4L, ND5, and ND6),…”