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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. Kovacs
Review

Abstract

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.

Keywords

Peroxisomes Autophagy Selective autophagy Pexophagy Yeast Mammalian Organelle 

Abbreviations

3AT

3-Amino-1-2-4-triazole

3-MA

3-Methyladenine

A11BR

Atg11-binding region

ABCD3

ATP-binding cassette subfamily D member 3

ACBD5

Acyl-CoA binding protein 5

AIM

Atg8-interacting motif

ALOX15

15-Lipoxygenase-1

AMPK

AMP-activated protein kinase

ATG

Autophagy-related gene

ATM

Ataxia-telangiectasia mutated

BNIP3

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

Caf4

CCR4-associated factor 4

CALCOCO2

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

ccRCC

Clear cell renal cell carcinoma

CHO

Chinese hamster ovary

Dnm1

Dynamin 1

ER

Endoplasmic reticulum

FUNDC1

FUN14 domain containing 1

GABARAP

γ-Aminobutyric acid receptor-associated protein

HIF

Hypoxia-inducible factor

Hrr25

Casein kinase 1δ homologue

LC3

Microtubule-associated protein-1 light chain 3

LIR

LC3-interacting regions

LKB1

Serine/threonine kinase 11

MAPL

Mitochondrial-anchored protein ligase

Mdv1

Mitochondrial division protein 1

MIPA

Micropexophagy-specific apparatus

mTORC1

Mechanistic target of rapamycin complex 1

Mul1

Mitochondrial-anchored protein ligase

Mulan

Mitochondrial-anchored protein ligase

NBR1

Neighbor of BRCA1 gene

NDP52

Nuclear dot protein 52 kDa

OMM

Outer mitochondrial membrane

OPTN

Optineurin

p62

Sequestosome 1

PARP

Poly(ADP-ribose) polymerase

PAS

Phagophore assembly site

PBD

Peroxisome biogenesis disorder

PE

Phosphatidylethanolamine

PEX

Peroxin

PGC-1α

PPAR gamma coactivator 1-alpha

PI3K

Phosphatidylinositol 3-kinase

PIK3R4

PI3K regulatory subunit 4

PINK1

PTEN-induced putative kinase 1

PMP

Peroxisomal membrane protein

PPARα

Peroxisome proliferator-activated receptor alpha

PTS1

Peroxisomal targeting signal 1

RHEB

RAS homolog enriched in brain

ROS

Reactive oxygen species

RPC

Receptor protein complex

SQSTM1

Sequestosome 1

TAX1BP1

Tax1-binding protein 1

TFEB

Transcription factor EB

TNKS

Tankyrase

TSC

Tuberous sclerosis complex

Ub

Ubiquitin

UBD

Ub-binding domain

ULK1/2

UNC-51-like kinase ½

USP30

Ubiquitin carboxyl-terminal hydrolase 30

VAPA/B

Vesicle-associated membrane protein-associated proteins A/B

VHL

Von Hippel–Lindau

Vps

Vacuolar protein sorting-associated protein

Notes

Acknowledgements

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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