Histochemistry and Cell Biology

, Volume 150, Issue 5, pp 473–488 | Cite as

Pexophagy in yeast and mammals: an update on mysteries

  • Tanja Eberhart
  • Werner J. KovacsEmail author


Peroxisomes are ubiquitous and highly dynamic organelles that play a central role in the metabolism of lipids and reactive oxygen species. The importance of peroxisomal metabolism is illustrated by severe peroxisome biogenesis disorders in which functional peroxisomes are absent or disorders caused by single peroxisomal enzyme deficiencies. These multisystemic diseases manifest specific clinical and biochemical disturbances that originate from the affected peroxisomal pathways. An emerging role of the peroxisome has been identified in many types of diseases, including cancer, neurodegenerative disorders, aging, obesity, and diabetes. Peroxisome homeostasis is achieved via a tightly regulated interplay between peroxisome biogenesis and degradation via selective autophagy, which is commonly known as “pexophagy”. Dysregulation of either peroxisome biogenesis or pexophagy may be detrimental to the health of cells and contribute to the pathophysiology of these diseases. Autophagy is an evolutionary conserved catabolic process for non-selective degradation of macromolecules and organelles in response to various stressors. In selective autophagy, specific cargo-recognizing receptors connect the cargo to the core autophagic machinery, and additional posttranslational modifications such as ubiquitination and phosphorylation regulate this process. Several stress conditions have been shown to stimulate pexophagy and decrease peroxisome abundance. However, our understanding of the mechanisms that particularly regulate mammalian pexophagy has been limited. In recent years considerable progress has been made uncovering signaling pathways, autophagy receptors and adaptors as well as posttranslational modifications involved in pexophagy. In this review, which is published back-to-back with a peroxisome review by Islinger et al. [(Histochem Cell Biol 137:547–574, 2018). The peroxisome: an update on mysteries 2.0], we focus on recent novel findings on the underlying molecular mechanisms of pexophagy in yeast and mammalian cells and highlight concerns and gaps in our knowledge.


Peroxisomes Autophagy Selective autophagy Pexophagy Yeast Mammalian Organelle 







Atg11-binding region


ATP-binding cassette subfamily D member 3


Acyl-CoA binding protein 5


Atg8-interacting motif




AMP-activated protein kinase


Autophagy-related gene


Ataxia-telangiectasia mutated


Bcl-2 and adenovirus E1B 19-kDa-interacting protein 3


CCR4-associated factor 4


Calcium-binding and coiled-coil domain-containing protein 2


Clear cell renal cell carcinoma


Chinese hamster ovary


Dynamin 1


Endoplasmic reticulum


FUN14 domain containing 1


γ-Aminobutyric acid receptor-associated protein


Hypoxia-inducible factor


Casein kinase 1δ homologue


Microtubule-associated protein-1 light chain 3


LC3-interacting regions


Serine/threonine kinase 11


Mitochondrial-anchored protein ligase


Mitochondrial division protein 1


Micropexophagy-specific apparatus


Mechanistic target of rapamycin complex 1


Mitochondrial-anchored protein ligase


Mitochondrial-anchored protein ligase


Neighbor of BRCA1 gene


Nuclear dot protein 52 kDa


Outer mitochondrial membrane




Sequestosome 1


Poly(ADP-ribose) polymerase


Phagophore assembly site


Peroxisome biogenesis disorder






PPAR gamma coactivator 1-alpha


Phosphatidylinositol 3-kinase


PI3K regulatory subunit 4


PTEN-induced putative kinase 1


Peroxisomal membrane protein


Peroxisome proliferator-activated receptor alpha


Peroxisomal targeting signal 1


RAS homolog enriched in brain


Reactive oxygen species


Receptor protein complex


Sequestosome 1


Tax1-binding protein 1


Transcription factor EB




Tuberous sclerosis complex




Ub-binding domain


UNC-51-like kinase ½


Ubiquitin carboxyl-terminal hydrolase 30


Vesicle-associated membrane protein-associated proteins A/B


Von Hippel–Lindau


Vacuolar protein sorting-associated protein



This work was supported by the Swiss National Science Foundation (SNSF) Grant 31003A_166245 to W.J.K.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Molecular Health SciencesETH ZurichZurichSwitzerland

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