Abstract
In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators in the regulation of cell death. In addition to apoptosis, necrosis is a highly relevant form of programmed liver cell death. Differential activation of specific forms of programmed cell death may not only affect the outcome of liver disease but may also provide new opportunities for therapeutic intervention. This review describes the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis. We focus on mitochondrial-driven apoptosis and current knowledge of necroptosis and discuss therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases.
Highlights
Cells undergo dynamic processes to maintain homeostasis, in response to internal and external “stressors,” which include drugs, viruses, and molecules produced in metabolic disorders
Mitochondrial fission may be integral to programmed cell death, which is required for the removal of fatally damaged cells, which have exceeded their adaptive capacity
Several studies have reported that members of the B cell lymphoma-2 (BCL-2) family drive mitochondrial outer membrane permeabilization (MOMP), resulting in the activation of apoptosis-inducing factor-dependent and caspase-dependent apoptotic cell death [5,6,7]
Summary
Cells undergo dynamic processes to maintain homeostasis, in response to internal and external “stressors,” which include drugs, viruses, and molecules produced in metabolic disorders. ROS production relies on mitochondria, TNF-induced necroptosis is inhibited in mitochondrial-deficient cells, suggesting that the production of mitochondrial ROS accompanies, but is not necessary for RIPK3-dependent necroptosis [13]. Both apoptotic and necroptotic cell death converge in mitochondria. We describe the dynamic behavior (fusion and fission) of mitochondria in response to stress and mitochondrial-mediated mechanisms of cell death. Using this information, we discuss strategies for the treatment of chronic liver diseases, liver fibrosis, and hepatocellular carcinoma (HCC)
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