The Role of Mitochondria in Liver Ischemia-Reperfusion Injury: From Aspects of Mitochondrial Oxidative Stress, Mitochondrial Fission, Mitochondrial Membrane Permeable Transport Pore Formation, Mitophagy, and Mitochondria-Related Protective Measures

Abstract

Ischemia-reperfusion injury (IRI) has indeed been shown as a main complication of hepatectomy, liver transplantation, trauma, and hypovolemic shock. A large number of studies have confirmed that microvascular and parenchymal damage is mainly caused by reactive oxygen species (ROS), which is considered to be a major risk factor for IRI. Under normal conditions, ROS as a kind of by-product of cellular metabolism can be controlled at normal levels. However, when IRI occurs, mitochondrial oxidative phosphorylation is inhibited. In addition, oxidative respiratory chain damage leads to massive consumption of adenosine triphosphate (ATP) and large amounts of ROS. Additionally, mitochondrial dysfunction is involved in various organs and tissues in IRI. On the one hand, excessive free radicals induce mitochondrial damage, for instance, mitochondrial structure, number, function, and energy metabolism. On the other hand, the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. According to the formation mechanism of IRI, various substances have been discovered or synthesized for specific targets and cell signaling pathways to inhibit or slow the damage of liver IRI to the body. Here, based on the development of this field, this review describes the role of mitochondria in liver IRI, from aspects of mitochondrial oxidative stress, mitochondrial fusion and fission, mPTP formation, and corresponding protective measures. Therefore, it may provide references for future clinical treatment and research.

Attenuation of hepatic ischemia‑reperfusion injury by adipose stem cell‑derived exosome treatment via ERK1/2 and GSK‑3β signaling pathways

“…The generation of reactive oxygen species (ROS), lipid peroxidation and dsDNA damage are prime mechanisms consequently associated to I/R injury ( 4 , 5 ). ROS generated by mitochondria and release of inflammatory mediators from the endoplasmic reticulum result in upregulation of autophagy-related genes ( 6 , 7 ). Several attempts have been made to control hepatic I/R injury.…”

Thioredoxin interacting protein protects mice from fasting induced liver steatosis by activating ER stress and its downstream signaling pathways

“…Dysregulation of enzymes involved in hepatic FA β-oxidation and/or FA synthesis leads to liver steatosis (LS) or fatty liver 2 , 3 . During fasting, mitochondria is damaged by enhanced generation of mitochondrial reactive oxygen species due to the reduction in available energy sources; therefore, clearing damaged mitochondria is important to promote β-oxidation 4 , 5 .…”

Mitochondria and their potential role in acute lung injury (Review)

“…Mitochondrial fission is a complex and multistep process that serves a crucial role in the regulatory mechanisms of cellular proliferation, differentiation, apoptosis, mitochondrial quality control and ROS production ( 84-87 ). For example, mitochondrial fission has been demonstrated to accelerate the segregation and autophagy of damaged mitochondria under stress conditions, which effectively reduces the accumulation of dysfunctional mitochondria and subsequently ameliorates the cellular stress conditions ( 88 ). The GTPase dynamin-related protein 1 (Drp1/DNM1L) is the primary driving factor of mitochondrial fission ( 89 ).…”