The mitochondrion is an organelle that plays a vital role in the regulation of hepatic cellular redox, lipid metabolism, and cell death. Mitochondrial dysfunction is associated with both acute and chronic liver diseases with emerging evidence indicating that mitophagy, a selective form of autophagy for damaged/excessive mitochondria, plays a key role in the liver’s physiology and pathophysiology. This review will focus on mitochondrial dynamics, mitophagy regulation, and their roles in various liver diseases (alcoholic liver disease, non-alcoholic fatty liver disease, drug-induced liver injury, hepatic ischemia-reperfusion injury, viral hepatitis, and cancer) with the hope that a better understanding of the molecular events and signaling pathways in mitophagy regulation will help identify promising targets for the future treatment of liver diseases.

Background and AimsLiver stiffness (LS) and spleen stiffness (SS) are two most widely accessible non-invasive parameters for predicting esophageal varices (EV), but the reported accuracy of the two predictors have been inconsistent across studies. This meta-analysis aims to evaluate the diagnostic performance of LS and SS measurement for detecting EV in patients with chronic liver disease (CLD), and compare their accuracy.MethodsPubmed/Medline, Embase, Cochrane Library and Ovid were searched for all studies assessing SS and LS simultaneously in EV diagnosis. A total of 16 studies including 1892 patients were included in this meta-analysis, and the pooled statistical parameters were calculated using the bivariate mixed effects models.ResultsIn detection of any EV, for LS measurement, the summary sensitivity was 0.83 (95% confidence interval [CI]: 0.78–0.87), and the specificity was 0.66 (95% CI: 0.60–0.72). While for SS measurement, the pooled sensitivity and specificity was 0.88 (95% CI: 0.83–0.92) and 0.78 (95% CI: 0.73–0.83). The summary receiver operating characteristic (SROC) curve values of LS and SS were 0.81 (95% CI: 0.77–0.84) and 0.88 (95% CI: 0.85–0.91) respectively, and the results had statistical significance (P<0.01). The diagnostic odds ratio (DOR) of SS (25.73) was significantly higher than that of LS (9.54), with the relative DOR value was 2.48 (95%CI: 1.10–5.60), P<0.05.ConclusionsUnder current techniques, SS is significantly superior to LS for identifying the presence of EV in patients with CLD. SS measurement may help to select patients for endoscopic screening.

Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. We investigated the role of PINK1-Parkin pathway in hepatocyte mitophagy in APAP-induced liver injury in mice. Wild-type (WT), PINK1 knockout (KO), Parkin KO, and PINK1 and Parkin double KO (DKO) mice were treated with APAP for different time points. Liver injury was determined by measuring serum alanine aminotransferase (ALT) activity, H&E staining as well as TUNEL staining of liver tissues. Tandem fluorescent-tagged inner mitochondrial membrane protein Cox8 (Cox8-GFP-mCherry) can be used to monitor mitophagy based on different pH stability of GFP and mCherry fluorescent proteins. We overexpressed Cox8-GFP-mCherry in mouse livers via tail vein injection of an adenovirus Cox8-GFP-mCherry. Mitophagy was assessed by confocal microscopy for Cox8-GFP-mCherry puncta, electron microscopy (EM) analysis for mitophagosomes and western blot analysis for mitochondrial proteins. Parkin KO and PINK1 KO mice improved the survival after treatment with APAP although the serum levels of ALT were not significantly different among PINK1 KO, Parkin KO and WT mice. We only found mild defects of mitophagy in PINK1 KO or Parkin KO mice after APAP, and improved survival in PINK1 KO and Parkin KO mice could be due to other functions of PINK1 and Parkin independent of mitophagy. In contrast, APAP-induced mitophagy was significantly impaired in PINK1-Parkin DKO mice. PINK1-Parkin DKO mice had further elevated serum levels of ALT and increased mortality after APAP administration. In conclusion, our results demonstrated that PINK1-Parkin signaling pathway plays a critical role in APAP-induced mitophagy and liver injury.