PINK1 Ameliorates Acute-on-chronic Liver Failure by Inhibiting Apoptosis Through MTORC2/AKT Signaling

Overview

Journal Cell Death Discov

Date 2022 Apr 24

PMID 35461334

Authors

Xuehong Yin

Ran Xue

Jing Wu

Muchen Wu

Bangxiang Xie

Qinghua Meng

Affiliations

Soon will be listed here.

Abstract

Acute-on-chronic liver failure (ACLF) is a lethal syndrome with a remarkable short-term death rate. Even worse, effective internal medicine therapies are currently lacking. Increasing evidence indicates apoptosis plays a critical role in the progression of liver failure. PINK1 has an essential function in maintaining cell survival. However, the role and underlying mechanism of PINK1 in apoptosis in ACLF are incompletely understood. Herein, our team discovered that PINK1 remarkably improved ACLF, featured by a reduction in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and an amelioration in the gross and microscopy histopathology appearance of hepatic tissues. Meanwhile, PINK1 affected cleaved caspase-3 expression via mTORC2/AKT, and this effect was eliminated after further intervention with Rictor or AKT. Overall, these findings indicate that PINK1 participates in the regulation of multiple biological functions, including hepatic cell growth and apoptosis in ACLF via the mTORC2/AKT signaling pathway. The present research offers a solid theory-wise foundation for the clinic applications of PINK1 as a valid target for ACLF treatment to reverse or postpone the development of ACLF.

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