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Excess Peroxisomes Are Degraded by Autophagic Machinery in Mammals
Abstract
Peroxisomes are degraded by autophagic machinery termed "pexophagy" in yeast; however, whether this is essential for peroxisome degradation in mammals remains unknown. Here we have shown that Atg7, an essential gene for autophagy, plays a pivotal role in the degradation of excess peroxisomes in mammals. Following induction of peroxisomes by a 2-week treatment with phthalate esters in control and Atg7-deficient livers, peroxisomal degradation was monitored within 1 week after discontinuation of phthalate esters. Although most of the excess peroxisomes in the control liver were selectively degraded within 1 week, this rapid removal was exclusively impaired in the mutant liver. Furthermore, morphological analysis revealed that surplus peroxisomes, but not mutant hepatocytes, were surrounded by autophagosomes in the control. Our results indicated that the autophagic machinery is essential for the selective clearance of excess peroxisomes in mammals. This is the first direct evidence for the contribution of autophagic machinery in peroxisomal degradation in mammals.
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“In other contexts, a robust loss of SQSTM1 does not correlate with increased autophagic flux as assessed by a luciferase-based measure of flux [338]; a decrease of SQSTM1 can even relate to a blockage of autophagy due to cleavage of the protein, together with other autophagy proteins, by caspases or calpains [562].”
From Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1 (2021) · cites this paper as [338]
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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
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Self-citationImpairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice
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Cited by
Sorted by citations
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
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Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
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Self-citationHomeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.
Komatsu, M., Waguri, S., Koike, M., Sou, Y.-S., Ueno, T., Hara, T., Mizushima, N., Iwata, J.-I., Ezaki, J., Murata, S., et al. (2007) · Cell · doi:10.1016/j.cell.2007.10.035 · Cited by 2,124
Self-citation
Metadata
- Authors
- Iwata, J.-I., Ezaki, J., Komatsu, M., Yokota, S., Ueno, T., Tanida, I., Chiba, T., Tanaka, K., & Kominami, E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 281
- Issue
- 7
- Pages
- 4035-4041
- ISSN
- 0021-9258
- Cited by
- 212
- References
- 4
- Language
- en
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