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.
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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
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This work was supported by the Swiss National Science Foundation (SNSF) Grant 31003A_166245 to W.J.K.
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Eberhart, T., Kovacs, W.J. Pexophagy in yeast and mammals: an update on mysteries. Histochem Cell Biol 150, 473–488 (2018). https://doi.org/10.1007/s00418-018-1724-3
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DOI: https://doi.org/10.1007/s00418-018-1724-3