Pex3-anchored Atg36 tags peroxisomes for degradation in Saccaromyces cerevisiae

Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, UK.
The EMBO Journal (Impact Factor: 10.43). 05/2012; 31(13):2852-68. DOI: 10.1038/emboj.2012.151
Source: PubMed


Peroxisomes undergo rapid, selective autophagic degradation (pexophagy) when the metabolic pathways they contain are no longer required for cellular metabolism. Pex3 is central to the formation of peroxisomes and their segregation because it recruits factors specific for these functions. Here, we describe a novel Saccharomyces cerevisiae protein that interacts with Pex3 at the peroxisomal membrane. We name this protein Atg36 as its absence blocks pexophagy, and its overexpression induces pexophagy. We have isolated pex3 alleles blocked specifically in pexophagy that cannot recruit Atg36 to peroxisomes. Atg36 is recruited to mitochondria if Pex3 is redirected there, where it restores mitophagy in cells lacking the mitophagy receptor Atg32. Furthermore, Atg36 binds Atg8 and the adaptor Atg11 that links receptors for selective types of autophagy to the core autophagy machinery. Atg36 delivers peroxisomes to the preautophagosomal structure before being internalised into the vacuole with peroxisomes. We conclude that Pex3 recruits the pexophagy receptor Atg36. This reinforces the pivotal role played by Pex3 in coordinating the size of the peroxisome pool, and establishes its role in pexophagy in S. cerevisiae.

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    • "was shown to be the adaptor for pexophagy, and was capable of interacting with Atg8, Atg11, and Pex3. [40]. Although this protein as a whole was not homologous to Atg30, both the AIM and 11-BS are conserved in Atg36 [38]. "
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    ABSTRACT: Pexophagy, selective degradation of peroxisomes via autophagy, is the main system for reducing organelle abundance. Elucidation of the molecular machinery of pexophagy has been pioneered in studies of the budding yeast Saccharomyces cerevisiae and the methylotrophic yeasts Pichia pastoris and Hansenula polymorpha. Recent analyses using these yeasts have elucidated the molecular machineries of pexophagy, especially in terms of the interactions and modifications of the so-called adaptor proteins required for guiding autophagic membrane biogenesis on the organelle surface. Based on the recent findings, functional relevance of pexophagy and another autophagic pathway, mitophagy (selective autophagy of mitochondria), is discussed. We also discuss the physiological importance of pexophagy in these yeast systems. This article is part of a Special Issue entitled: Peroxisomes.
    Biochimica et Biophysica Acta 09/2015; DOI:10.1016/j.bbamcr.2015.09.023 · 4.66 Impact Factor
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    • "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 ) . Surprisingly , Atg30 and Atg36 display no similarities at the amino acid level even though they exhibit similar function ( Van der Zand and Reggiori , 2012 ) . In"
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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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    • "gradation when the organelles are no longer required ( Iwata et al . , 2006 ; Farré et al . , 2008 ; Motley et al . , 2012 ) . The pexophagy receptors Atg30 and Atg36 were identified in P . pastoris and S . cerevisiae , respectively , and their overexpression stimulates pexophagy even under peroxisome - inducing conditions ( Farré et al . , 2008 ; Motley et al . , 2012 ) . Their synthesis is upregulated in peroxisome proliferation conditions , they"
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    Frontiers in Cell and Developmental Biology 08/2015; 3:42. DOI:10.3389/fcell.2015.00042
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