Catalase deficiency induces reactive oxygen species mediated pexophagy and cell death in the liver during prolonged fasting.

Abstract

Peroxisomes are dynamic organelles that participate in a diverse array of cellular processes, including β-oxidation, which produces a considerable amount of reactive oxygen species (ROS). Although we showed that catalase depletion induces ROS-mediated pexophagy in cells, the effect of catalase deficiency during conditions that favor ROS generation remains elusive in mice. In this study, we reported that prolonged fasting in catalase-knockout (KO) mice drastically increased ROS production, which induced liver-specific pexophagy, an autophagic degradation of peroxisomes. In addition, increased ROS generation induced the production of pro-inflammatory cytokines in the liver tissues of catalase-KO mice. Furthermore, there was a significant increase in the levels of aspartate transaminase and alanine transaminase as well as apparent cell death in the liver of catalase-KO mice during prolonged fasting. However, an intra-peritoneal injection of the antioxidant N-acetyl-l-cysteine (NAC) and autophagy inhibitor chloroquine inhibited the inflammatory response, liver damage, and pexophagy in the liver of catalase-KO mice during prolonged fasting. Consistently, genetic ablation of autophagy, Atg5 led to suppression of pexophagy during catalase inhibition by 3-aminotriazole (3AT). Moreover, treatment with chloroquine also ameliorated the inflammatory response and cell death in embryonic fibroblast cells from catalase-KO mice. Taken together, our data suggest that ROS-mediated liver-specific pexophagy observed during prolonged fasting in catalase-KO mice may be responsible for the process associated with hepatic cell death.

• Authors: Raghbendra Kumar Dutta, Yunash Maharjan, Joon No Lee, Channy Park, Ye-Shih Ho, Raekil Park
• Journal: BioFactors (Oxford, England) (Biofactors) Vol. 47 Issue 1 Pg. 112-125 (Jan 2021) ISSN: 1872-8081 [Electronic] Netherlands
• PMID: 33496364 (Publication Type: Journal Article)
• Copyright: © 2021 International Union of Biochemistry and Molecular Biology.

Chemical References

• Reactive Oxygen Species
• Catalase
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Animals
• Catalase (genetics, physiology)
• Cells, Cultured
• Food Deprivation
• Hepatitis (drug therapy, etiology, metabolism, pathology)
• Liver (metabolism, pathology)
• Macroautophagy
• Mice, Knockout
• Peroxisomes
• Reactive Oxygen Species (metabolism)