Pexophagy: The Selective Degradation of Peroxisomes

Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322, USA.
International Journal of Cell Biology 03/2012; 2012(2):512721. DOI: 10.1155/2012/512721
Source: PubMed


Peroxisomes are single-membrane-bounded organelles present in the majority of eukaryotic cells. Despite the existence of great diversity among different species, cell types, and under different environmental conditions, peroxisomes contain enzymes involved in β-oxidation of fatty acids and the generation, as well as detoxification, of hydrogen peroxide. The exigency of all eukaryotic cells to quickly adapt to different environmental factors requires the ability to precisely and efficiently control peroxisome number and functionality. Peroxisome homeostasis is achieved by the counterbalance between organelle biogenesis and degradation. The selective degradation of superfluous or damaged peroxisomes is facilitated by several tightly regulated pathways. The most prominent peroxisome degradation system uses components of the general autophagy core machinery and is therefore referred to as "pexophagy." In this paper we focus on recent developments in pexophagy and provide an overview of current knowledge and future challenges in the field. We compare different modes of pexophagy and mention shared and distinct features of pexophagy in yeast model systems, mammalian cells, and other organisms.

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    • "et al . , 2011 ; Bernard and Klionsky , 2013 ; Hamasaki et al . , 2013 ) . In yeast the mechanism of recognition of specific cargo for both pexophagy and mitophagy is well understood . For methylotrophic yeasts ( e . g . , P . pastoris ) the pexophagy receptor is Atg30 , which interacts with peroxisomal membrane proteins Pex3 , Pex14 , and Atg37 ( Till et al . , 2012 ; Nazarko , 2014 ) . However , for S . cerevisiae and related yeasts the pexophagy receptor is Atg36 and appears to interact solely with Pex3 ( Motley et al . , 2012 ) . Both Atg30 and Atg36 need to be activated by phosphorylation in order to interact with the scaffold protein Atg11 and the autophagosome via Atg8 ( Farré et al . , 2013 )"
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    ABSTRACT: Membrane-bound organelles such as mitochondria, peroxisomes, or the endoplasmic reticulum (ER) create distinct environments to promote specific cellular tasks such as ATP production, lipid breakdown, or protein export. During recent years, it has become evident that organelles are integrated into cellular networks regulating metabolism, intracellular signaling, cellular maintenance, cell fate decision, and pathogen defence. In order to facilitate such signaling events, specialized membrane regions between apposing organelles bear distinct sets of proteins to enable tethering and exchange of metabolites and signaling molecules. Such membrane associations between the mitochondria and a specialized site of the ER, the mitochondria associated-membrane (MAM), as well as between the ER and the plasma membrane (PAM) have been partially characterized at the molecular level. However, historical and recent observations imply that other organelles like peroxisomes, lysosomes, and lipid droplets might also be involved in the formation of such apposing membrane contact sites. Alternatively, reports on so-called mitochondria derived-vesicles (MDV) suggest alternative mechanisms of organelle interaction. Moreover, maintenance of cellular homeostasis requires the precise removal of aged organelles by autophagy-a process which involves the detection of ubiquitinated organelle proteins by the autophagosome membrane, representing another site of membrane associated-signaling. This review will summarize the available data on the existence and composition of organelle contact sites and the molecular specializations each site uses in order to provide a timely overview on the potential functions of organelle interaction.
    Frontiers in Cell and Developmental Biology 09/2015; 3. DOI:10.3389/fcell.2015.00056
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    • "In this process, numerous new organelles are produced from pre-existing peroxisomes. When fatty acids are depleted from the medium, or after re-introduction of glucose, peroxisomes are degraded via the vacuole by pexophagy [5]. Pex11 is the peroxin (i.e. a protein involved in biogenesis or organization of peroxisomes) whose activity is required for the tubulation and fission of the single peroxisomal membrane during peroxisome proliferation. "
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    ABSTRACT: Pex11 is a peroxin that regulates the number of peroxisomes in eukaryotic cells. Recently it was found that a mutation in one of the three mammalian paralogs, PEX11β, results in a neurological disorder. The molecular function of Pex11, however, is not known. Saccharomyces cerevisiae Pex11 has been shown to recruit to peroxisomes the mitochondrial fission machinery, thus enabling proliferation of peroxisomes. This process is essential for efficient fatty acid β-oxidation. In this study, we used high-content microscopy on a genome-wide scale to determine the subcellular localization pattern of yeast Pex11 in all non-essential gene deletion mutants, and in temperature sensitive essential gene mutants. Pex11 localization and morphology of peroxisomes was profoundly affected by mutations in 104 different genes that were functionally classified. A group of genes encompassing MDM10, MDM12 and MDM34 that encode the mitochondrial and cytosolic components of the ERMES complex was analyzed in greater detail. Deletion of these genes caused a specifically altered Pex11 localization pattern, whereas deletion of MMM1, the gene encoding the fourth, endoplasmic reticulum-associated component of the complex, did not result in an altered Pex11 localization or peroxisome morphology phenotype. Moreover, we found that Pex11 and Mdm34 physically interact and that Pex11 plays a role in establishing the contact sites between peroxisomes and mitochondria through the ERMES complex. Based on these results we propose that the mitochondrial/cytosolic components of the ERMES complex establish a direct interaction between mitochondria and peroxisomes through Pex11. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Molecular Biology 03/2015; 14(11). DOI:10.1016/j.jmb.2015.03.004 · 4.33 Impact Factor
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    • "Different terms were coined to distinguish between different targets. The most investigated processes are mitophagy: the selective removal of defective or excess mitochondria [33]; aggrephagy: the disposal of aberrant, misfolded protein aggregates [34]; xenophagy: the selective autophagy of pathogenic intracellular bacteria, protozoa, or viruses [35, 36], and pexophagy: peroxisome autophagy first described in detail during peroxisome degradation in methylotrophic yeast species but also responsible for the destruction of 70–80% of the peroxisomal mass in mammalian cells [37]. The selective nature of autophagy is ensured mainly by specific adaptors, but direct interactions between the target molecule and the core autophagy machinery are also observed. "
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    ABSTRACT: The ubiquitin-proteasome system and autophagy were long viewed as independent, parallel degradation systems with no point of intersection. By now we know that these degradation pathways share certain substrates and regulatory molecules and show coordinated and compensatory function. Two ubiquitin-like protein conjugation pathways were discovered that are required for autophagosome biogenesis: the Atg12-Atg5-Atg16 and Atg8 systems. Autophagy has been considered to be essentially a nonselective process, but it turned out to be at least partially selective. Selective substrates of autophagy include damaged mitochondria, intracellular pathogens, and even a subset of cytosolic proteins with the help of ubiquitin-binding autophagic adaptors, such as p62/SQSTM1, NBR1, NDP52, and Optineurin. These proteins selectively recognize autophagic cargo and mediate its engulfment into autophagosomes by binding to the small ubiquitin-like modifiers that belong to the Atg8/LC3 family.
    BioMed Research International 06/2014; 2014(1):832704. DOI:10.1155/2014/832704 · 2.71 Impact Factor
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