Mitochondrial Dysfunction and Oxidative Stress in Liver Transplantation and Underlying Diseases: New Insights and Therapeutics

Abstract

Mitochondria are essential organelles for cellular energy and metabolism. Like with any organ, the liver highly depends on the function of these cellular powerhouses. Hepatotoxic insults often lead to an impairment of mitochondrial activity and an increase in oxidative stress, thereby compromising the metabolic and synthetic functions. Mitochondria play a critical role in ATP synthesis and the production or scavenging of free radicals. Mitochondria orchestrate many cellular signaling pathways involved in the regulation of cell death, metabolism, cell division, and progenitor cell differentiation. Mitochondrial dysfunction and oxidative stress are closely associated with ischemia-reperfusion injury during organ transplantation and with different liver diseases, including cholestasis, steatosis, viral hepatitis, and drug-induced liver injury. To develop novel mitochondria-targeting therapies or interventions, a better understanding of mitochondrial dysfunction and oxidative stress in hepatic pathogenesis is very much needed. Therapies targeting mitochondria impairment and oxidative imbalance in liver diseases have been extensively studied in preclinical and clinical research. In this review, we provide an overview of how oxidative stress and mitochondrial dysfunction affect liver diseases and liver transplantation. Furthermore, we summarize recent developments of antioxidant and mitochondria-targeted interventions.

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

“…Damaged mitochondrial outer membrane proteins could be degraded by proteasomes or be cleared by mitochondrial autophagy. Mitochondria sustain the integrity of structure and function through continuous fusion and fission [39,40]. Mitochondrial quality control (QC) is essential for regulating mitochondrial balance, which can be achieved through a series of processes such as mitochondrial fusion, fission, and selective mitochondrial autophagy [41][42][43].…”

“…Damaged mitochondrial outer membrane proteins could be degraded by proteasomes or be cleared by mitochondrial autophagy. Mitochondria sustain the integrity of structure and function through continuous fusion and fission [ 39 , 40 ].…”

HAX1 maintains the glioma progression in hypoxia through promoting mitochondrial fission

“…Mitochondria maintain structural and functional integrity through continuous fusion and fission. 28 , 29 Therefore, mitochondrial fission is very important for the integrity of mitochondria. The promotion of mitochondrial fission can enhance tumour malignancy of cancer cells.…”

Self-sorting assembly of artificial building blocks

“…Highly specific and architected supramolecular structures have existed since the appearance of living beings, and are crucial for maintaining life processes. [1][2][3][4][5] Although the bio-substances, including nucleic acids, peptides, phospholipids, etc., are extremely crowded in cells, they are all able to self-organize selectively into hierarchical structures, instead of forming random aggregates of mixtures. This so-called self-sorting assembly behaviour is essentially important for the realization of proper biological functions.…”