{'fraction_non_alphanumeric': 0.03543307086614173, 'fraction_numerical': 0.006889763779527559, 'mean_word_length': 5.413249211356467, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
PINK1 Activation and Translocation to Mitochondria-Associated Membranes Mediates Mitophagy and Protects Against Hepatic Ischemia/Reperfusion Injury.

Hepatic ischemia/reperfusion (I/R) injury is a major concern in liver surgery settings. Mitochondria are critical targets or the origin of tissue injury, particularly I/R injury. Mitophagy, a selective form of autophagy, is a fundamental process that removes damaged or unwanted mitochondria for mitochondrial quality control, but its role in hepatic I/R remains unclear. In the present study, we investigated the role of mitophagy in hepatic I/R by focusing on PTEN-induced putative kinase 1 (PINK1). Livers from 10-week-old mice and primary hepatocytes were subjected to in vivo hepatic I/R and in vitro hypoxia-reoxygenation (H/R), respectively. Analyses of oxidative stress, immunoblotting and ATP generation showed that hepatic I/R leads to mitochondrial damage. Dysfunctional mitochondria promoted reactive oxygen species (ROS) production and apoptosis. Hepatic I/R led to decreases in the mitochondrial proteins COX4 and TOM20 and mitochondrial DNA (mtDNA) and increases in the autophagy related indicators LC3 and P62, which indicates that hepatic I/R promotes mitophagy. We found that I/R also leads to endoplasmic reticulum (ER) stress, which has frequent signal communication with mitochondria through the mitochondria-associated membranes (MAMs). We showed that the mitophagy-related proteins Parkin, Beclin, optineurin (OPTN) were enhanced in hepatic I/R. No significant change in PINK1 but it translocated to MAMs region to initiate mitophagy. The silencing PINK1 by shRNA in cultured primary hepatocytes reduced the level of H/R-induced mitophagy, leading to the accumulation of dysfunctional mitochondria during H/R, increased production of ROS, mitochondria-induced apoptosis, and eventually hepatocyte death. Taken together, these findings indicate that PINK1-mediated mitophagy plays a key role in mitochondrial quality control and liver cell survival during I/R.