Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases

Abstract

The liver is a vital metabolic and detoxifying organ and suffers diverse endogenous or exogenous damage. Hepatocyte mitochondria experience various structural and functional defects from liver injury, bearing oxidative stress, metabolic dysregulation, and the disturbance of mitochondrial quality control (MQC) mechanisms. Mitochondrial malfunction initiates the mitochondria-mediated apoptotic pathways and the release of damage signals, aggravating liver damage and disease progression via inflammation and reparative fibrogenesis. Removal of mitochondrial impairment or the improvement of MQC mechanisms restore mitochondrial homeostasis and benefit liver health. This review discusses the association of mitochondrial disorders with hepatic pathophysiological processes and the resultant potential of mitochondrion-targeting therapeutics for hepatic disorders. The recent advances in the MQC mechanisms and the mitochondrial-derived damage-associated molecular patterns (DAMPs) in the pathology and treatment of liver disease are particularly focussed.

Keywords:

• Mitochondrial dysfunction
• mitochondrion-targeting
• oxidative stress
• MQC mechanisms
• mtDAMPs
• liver disease
• therapeutics

Disclosure statement

No potential conflict of interest was reported by the author(s).

Table 1. The pathways of mitochondrial dysfunction.

Additional information

Funding

This work was supported by National Natural Science Foundation of China [81371675].