Catalase inhibition induces pexophagy through ROS accumulation
- Department of Biomedical Science & Engineering, Gwangju Institute of Science & Technology, Gwangju 61005 (Korea, Republic of)
- Department of Microbiology and Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan, Jeonbuk 54538 (Korea, Republic of)
- Graduate School of East-West Medical Science, Kyung-Hee University, Yongin 17104 (Korea, Republic of)
Highlights: • Catalase deficiency or its inhibition by 3 A T during serum starvation results in pexophagy. • Pexophagy mediated by catalase inhibition is accompanied by PEX5 ubiquitination. • ROS accumulation in peroxisome is the key factor to induce pexophagy. • N-acetyl-l-cysteine prevents ROS-mediated pexophagy. Peroxisomes are dynamic and multifunctional organelles involved in various cellular metabolic processes, and their numbers are tightly regulated by pexophagy, a selective degradation of peroxisomes through autophagy to maintain peroxisome homeostasis in cells. Catalase, a major peroxisome protein, plays a critical role in removing peroxisome-generated reactive oxygen species (ROS) produced by peroxisome enzymes, but the contribution of catalase to pexophagy has not been reported. Here, we investigated the role of catalase in peroxisome degradation during nutrient deprivation. Both short interfering RNA-mediated silencing of catalase and pharmacological inhibition by 3-aminotriazole (3AT) decreased the number of peroxisomes and resulted in the downregulation of peroxisomal proteins, such as PMP70 and PEX14 under serum starvation. In addition, treatment with 3AT induced NBR1-dependent autophagy and PEX5 ubiquitination in the absence of serum, which was accompanied by accumulation of ROS. Co-treatment with antioxidant agent N-acetyl-l-cysteine (NAC) prevented ROS accumulation and pexophagy by modulating peroxisome protein levels and the association of NBR1, a pexophagy receptor with peroxisomes. Taken together, these findings demonstrate that catalase plays an important role in pexophagy during nutrient deprivation.
- OSTI ID:
- 23125064
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 501, Issue 3; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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