Pexophagy: Autophagic degradation of peroxisomes

Sakai, Yasuyoshi; Oku, Masahide; Klei, Ida J. van der; Kiel, Jan A.K.W.

doi:10.1016/j.bbamcr.2006.08.023

Cited by 207 publications

(194 citation statements)

References 59 publications

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“…In this regard, the structures observed in the VE appeared to be selective for endosomes with minimum amounts of cytosol, judging from the electron micrographs and fluorescence images. The endosomeapical vacuole interaction resembled pexophagy in yeast cells, by which peroxisomes are internalised by digestive vacuoles in response to the nutritional conditions 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Cargo delivery may occur via a completely different mechanism known as microautophagy, in which lysosomes take up other organelles and/or cytosol directly by encircling the targets with lysosomal membrane. In yeast cells, peroxisomes are degraded via microautophagy in response to nutrient availability 18 . Mitochondria are also well-known substrates for microautophagic degradation 19 .…”

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confidence: 99%

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Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos

et al. 2012

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The differentiation and patterning of murine early embryos are sustained by the visceral endoderm, an epithelial layer of polarised cells that has critical roles in multiple signalling pathways and nutrient uptake. Both nutritional and signalling functions rely upon the endocytosis of various molecules from the cell surface via the endocytic pathway. However, endocytic membrane dynamics in this embryonic tissue remain poorly understood. Here we show that the functions of rab7, a small GTP-binding protein regulating the late endocytic pathway, are essential for embryonic patterning during gastrulation. The endosomes of visceral endoderm cells are delivered via a unique microautophagy-like process to the apical vacuole, a large compartment exhibiting lysosomal characteristics. Loss of rab7 function results in severe inhibition of this endocytic pathway. our results indicate that the microautophagic process and flow of the endocytic membrane have essential roles in early embryonic development.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos

et al. 2012

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“…5A, top panels), although not a frequent observation, could reflect this. Selective forms of microautophagy in yeast are, however, thought to require the core autophagy machinery, including ATG5, [43][44][45] thus could not operate in the Datg5 cells. Nonselective microautophagy has been reported not to require ATG5 46,47 and so this pathway could occur in the Datg5 Leishmania.…”

Section: Discussionmentioning

confidence: 99%

Glycosome turnover inLeishmania majoris mediated by autophagy

et al. 2014

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Abbreviations: ATG, autophagy-related; GFP, green fluorescent protein; mC, mCherry fluorescent protein; MVT, multivesicular tubule; RFP, red fluorescent protein; TEM, transmission electron microscopy.Autophagy is a central process behind the cellular remodeling that occurs during differentiation of Leishmania, yet the cargo of the protozoan parasite's autophagosome is unknown. We have identified glycosomes, peroxisome-like organelles that uniquely compartmentalize glycolytic and other metabolic enzymes in Leishmania and other kinetoplastid parasitic protozoa, as autophagosome cargo. It has been proposed that the number of glycosomes and their content change during the Leishmania life cycle as a key adaptation to the different environments encountered. Quantification of RFP-SQL-labeled glycosomes showed that promastigotes of L. major possess »20 glycosomes per cell, whereas amastigotes contain »10. Glycosome numbers were significantly greater in promastigotes and amastigotes of autophagy-defective L. major Datg5 mutants, implicating autophagy in glycosome homeostasis and providing a partial explanation for the previously observed growth and virulence defects of these mutants. Use of GFP-ATG8 to label autophagosomes showed glycosomes to be cargo in »15% of them; glycosome-containing autophagosomes were trafficked to the lysosome for degradation. The number of autophagosomes increased 10-fold during differentiation, yet the percentage of glycosome-containing autophagosomes remained constant. This indicates that increased turnover of glycosomes was due to an overall increase in autophagy, rather than an upregulation of autophagosomes containing this cargo. Mitophagy of the single mitochondrion was not observed in L. major during normal growth or differentiation; however, mitochondrial remnants resulting from stress-induced fragmentation colocalized with autophagosomes and lysosomes, indicating that autophagy is used to recycle these damaged organelles. These data show that autophagy in Leishmania has a central role not only in maintaining cellular homeostasis and recycling damaged organelles but crucially in the adaptation to environmental change through the turnover of glycosomes.

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“…Most peroxisomal ROS are detoxified by catalase and the ascorbate-glutathione cycle (4); however, some ROS inevitably damage peroxisomal proteins (5). Mechanisms for detecting and eliminating damaged peroxisomal proteins have not been described; however, removal of excess or nonfunctional peroxisomes in yeast and mammals can occur through pexophagy, a specialized form of autophagy (6). Although autophagy occurs in plants (7), plant pexophagy has not been reported.…”

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confidence: 99%

Peroxisome-associated matrix protein degradation in Arabidopsis

Lingard

Monroe-Augustus

Bartel

2009

Proc. Natl. Acad. Sci. U.S.A.

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Peroxisomes are ubiquitous eukaryotic organelles housing diverse enzymatic reactions, including several that produce toxic reactive oxygen species. Although understanding of the mechanisms whereby enzymes enter peroxisomes with the help of peroxin (PEX) proteins is increasing, mechanisms by which damaged or obsolete peroxisomal proteins are degraded are not understood. We have exploited unique aspects of plant development to characterize peroxisome-associated protein degradation (PexAD) in Arabidopsis. Oilseed seedlings undergo a developmentally regulated remodeling of peroxisomal matrix protein composition in which the glyoxylate cycle enzymes isocitrate lyase (ICL) and malate synthase (MLS) are replaced by photorespiration enzymes. We found that mutations expected to increase or decrease peroxisomal H2O2 levels accelerated or delayed ICL and MLS disappearance, respectively, suggesting that oxidative damage promotes peroxisomal protein degradation. ICL, MLS, and the ␤-oxidation enzyme thiolase were stabilized in the pex4 -1 pex22-1 double mutant, which is defective in a peroxisome-associated ubiquitin-conjugating enzyme and its membrane tether. Moreover, the stabilized ICL, thiolase, and an ICL-GFP reporter remained peroxisome associated in pex4 -1 pex22-1. ICL also was stabilized and peroxisome associated in pex6 -1, a mutant defective in a peroxisome-tethered ATPase. ICL and thiolase were mislocalized to the cytosol but only ICL was stabilized in pex5-10, a mutant defective in a matrix protein import receptor, suggesting that peroxisome entry is necessary for degradation of certain matrix proteins. Together, our data reveal new roles for PEX4, PEX5, PEX6, and PEX22 in PexAD of damaged or obsolete matrix proteins in addition to their canonical roles in peroxisome biogenesis.Arabidopsis thaliana ͉ organelle remodeling ͉ peroxisome ͉ protein turnover P eroxisomes are ubiquitous eukaryotic organelles that characteristically possess H 2 O 2 -producing oxidases and H 2 O 2 -decomposing catalases. Specific reactions housed in peroxisomes vary by species, developmental stage, and cell type. For example, young seedling peroxisomes contain glyoxylate cycle enzymes, whereas mature leaf peroxisomes contain photorespiration enzymes (1). Peroxisomal proteins are nuclearly encoded and inserted posttranslationally into the peroxisome matrix or membrane with the assistance of peroxins (peroxisome biogenesis proteins) (2, 3). Although matrix protein import into peroxisomes is increasingly understood, mechanisms for recognizing and eliminating damaged or obsolete peroxisomal proteins remain largely obscure. Damage to peroxisomal proteins can occur through interactions with reactive oxygen species (ROS) produced by peroxisomal oxidative reactions. Most peroxisomal ROS are detoxified by catalase and the ascorbate-glutathione cycle (4); however, some ROS inevitably damage peroxisomal proteins (5). Mechanisms for detecting and eliminating damaged peroxisomal proteins have not been described; however, removal of excess or nonfunctio...

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Pexophagy: Autophagic degradation of peroxisomes

Cited by 207 publications

References 59 publications

Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos

Delivery of endosomes to lysosomes via microautophagy in the visceral endoderm of mouse embryos

Glycosome turnover inLeishmania majoris mediated by autophagy

Peroxisome-associated matrix protein degradation in Arabidopsis

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