Emerging roles of mitochondria and autophagy in liver injury during sepsis
Authors:Toshihiko Aki1,*, Kana Unuma1 and Koichi Uemura1
1 Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.
Keywords:
autophagy, mitophagy, non-canonical autophagy, sepsis, mitochondrial dysfunction, liver, immune response, secretion.
Abbreviations:
ALT – alanine transaminase,
ATG – autophagy related,
ATP – adenosine triphosphate,
CLP – cecal ligation and puncture,
CPS-1 – carbamoylphosphat synthase,
GSDM – gasdermin,
IL – interleukin,
KO – knock out,
LPS – lipopolysaccharide,
NAAP – nicotic acid adenine dinucleotide phosphate,
PI3K – phosphatidylinositol-3-kinase,
ROS – reactive oxygen species,
TLR – toll-like receptor,
TNF – tumor necrosis factor,
ULK – Unc-51-like kinase,
WT – wild type.
Corresponding Author(s):
Conflict of interest statement:
The authors declare that there is no conflict of interest to disclose.
Please cite this article as:
Toshihiko Aki, Kana Unuma and Koichi Uemura (2017). Emerging roles of mitochondria and autophagy in liver injury during sepsis. Cell Stress 1(2): 79-89. doi: 10.15698/cst2017.11.110
© 2017 Aki et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Recent research indicates crucial roles of autophagy during sepsis. In animal models of sepsis induced by cecal ligation and puncture (CLP) or the systemic administration of lipopolysaccharides (LPS), autophagy is implicated in the activation and/or damage of various cells/organs, such as immune cells, heart, lung, kidney, and liver. Since sepsis is associated with an increased production of pro- as well as anti-inflammatory cytokines, it has long been considered that hypercytokinemia is a fetal immune response leading to multiple organ failure (MOF) and mortality of humans during sepsis. However, a recent paradigm illuminates the crucial roles of mitochondrial dysfunction as well as the perturbation of autophagy in the pathogenesis of sepsis. In the livers of animal models of sepsis, autophagy is involved in the elimination of damaged mitochondria to prevent the generation of mitochondrial ROS and the initiation of the mitochondrial apoptotic pathway. In addition, many reports now indicate that the role of autophagy is not restricted to the elimination of hazardous malfunctioning mitochondria within the cells; autophagy has been shown to be involved in the regulation of inflammasome activation and the release of cytokines as well as other inflammatory substances. In this review, we summarize recent literature describing the versatile role of autophagy and its possible implications in the pathogenesis of sepsis in the liver.