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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Available from: Andreas Till
    • "Autophagy is a degradation pathway existing in all eukaryotic organisms. It is the main system for the degradation of bulk cytoplasmic components in cells (Feng et al., 2014), but it also plays a crucial role in other processes, as immunity (Wileman, 2013), mitochondrial (Dengjel and Abeliovich, 2014) and peroxisomal (Till et al., 2012) degradation and clearance of misfolded protein aggregates (Lamark and Johansen, 2012). These pathways of selective autophagy, in contrast to the more or less random sequestration of cytosol components produced by the bulk autophagy, are regulated by the participation of specific adaptors. "
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    • "Peroxisomes are cell organelles found in virtually all multi-cellular organisms and comprise a separate cellular compartment whose main functions include the sequestration of metabolic processes that would otherwise be toxic to the cell, as well as the biosynthesis of several essential lipids [1]. The maintenance of the peroxisomal system involves several processes like peroxisome biogenesis, peroxisome growth and division [2] [3] [4] and turnover of peroxisomes by autophagy [5] [6] [7]. One of the most critical steps in peroxisome biogenesis is the correct spatial and temporal topogenesis of peroxisomal membrane proteins (PMPs) on the peroxisomal membrane. "
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    ABSTRACT: The correct topogenesis of peroxisomal membrane proteins is a crucial step for the formation of functioning peroxisomes. Although this process has been widely studied, the exact mechanism with which it occurs has not yet been fully characterized. Nevertheless, it is generally accepted that peroxisomes employ three proteins - Pex3, Pex19 and Pex16 in mammals - for the insertion of peroxisomal membrane proteins into the peroxisomal membrane. Structural biology approaches have been utilized for the elucidation of the mechanistic questions of peroxisome biogenesis, mainly by providing information on the architecture of the proteins significant for this process. This review aims to summarize, compare and put into perspective the structural knowledge that has been generated mainly for Pex3 and Pex19 and their interaction partners in recent years.
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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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