Trends in Molecular Medicine
Volume 26, Issue 2,
, Pages 201-214
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Peroxisomes share extensive metabolic connections with other cell organelles. Membrane contact sites (MCSs) establish and maintain such interactions, and they are vital for organelle positioning and motility. In the past few years peroxisome interactions and MCSs with other cellular organelles have been explored extensively, resulting in the identification of new MCSs, the tethering molecules involved, and their functional characterization. Defective tethering and compartmental communication can lead to pathological conditions that can be termed ‘organelle interaction diseases’. We review peroxisome–organelle interactions in mammals and summarize the most recent knowledge of mammalian peroxisomal organelle contacts in health and disease.
Peroxisomes: Small Cell Organelles in Need of Contact
Peroxisomes participate in a surprising variety of metabolic pathways. They are crucial for fatty acid (FA) catabolism and anabolism, for ether lipid and bile acid biosynthesis, and the metabolism of D-amino acids and of reactive oxygen species (ROS) including hydrogen peroxide produced by peroxisomal lipid oxidation. Most of these pathways with peroxisome involvement require close interaction with other organelles, such as mitochondria and the endoplasmic reticulum (ER), and proximity between
Peroxisomal Channels and Transporters
Owing to their small size (diameter of 100nm in fibroblasts ), peroxisomes can easily locate between larger organelles. Because vital metabolic pathways are only partially located in peroxisomes, tight cooperation between peroxisomes and other organelles is essential to ensure efficient transport of substrates (Figure1). This can be achieved by vesicular transfer, soluble lipid-transfer proteins , or via MCSs. Vesicular transfer supports peroxisome biogenesis through ER- and
Peroxisomal Contact Sites
It is currently believed that most if not all organelles form MCSs. MCSs are characterized by closeproximity of organelles, typically <30nm. They are established and stabilized by tethering proteins and/or lipids on the opposing membranes 2, 8, 11. MCSs facilitate communication between organelles and thus define functional relationships among intracellular compartments, thereby fine-tuning the balance between autonomy and interdependence of individual compartments. Because MCSs represent
Peroxisome–Organelle Interaction Diseases
A growing number of genetic factors have been linked to human disorders, and the definitions of disease entities are constantly shifting from symptoms to molecular parameters. Within molecular medicine, an improved understanding of the molecular and organellar networks makes it possible to identify or characterize new disease entities that are not primarily caused by defects in individual cell organelles but instead depend on the interaction of membrane compartments. In view of this
When we addressed the topic of organelle interaction a decade ago, stating that 'peroxisomes are no longer regarded as autonomous organelles because evidence for their interplay with other cellular organelles is emerging' , we stood at the beginning of the era of molecular understanding of organelle contacts. Over recent years we have witnessed the amazing discovery of the first MCS molecules. Now that the underlying premise of the existence and the multitude of organelle interactions is
We thank Sabine Grønborg, Markus Islinger, Henry Klemp, and Noa Lipstein for comments on the manuscript. We gratefully acknowledge grants from the Deutsche Forschungsgemeinschaft (DFG; SFB 1002/2 and TP A10 to S.T.), the Ministerium für Wissenschaft und Kultur (MWK)/VolkswagenStiftung (project 131260/ZN2921 to S.T.), and the Deutscher Akademischer Austauschdienst (DAAD; program 57381412 ID 91572398 to Y.S.).
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- Leigh disease
- also known as subacute necrotizing encephalomyelopathy, a neurometabolic multiorgan disorder caused by defects in mitochondrial function.
- Leydig cells
- cells located in the connective tissue surrounding the seminiferous tubules in the testicle. They produce testosterone, the male sex hormone
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Biochim. Biophys. Acta Rev. Cancer
- E. Dixit
Peroxisomes are signaling platforms for antiviral innate immunity
- M. Mattiazzi Ušaj
Genome-wide localization study of yeast Pex11 identifies peroxisome–mitochondria interactions through the ERMES complex
- G. Reiser
Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment
Int. J. Dev. Neurosci.
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Mitochondrial dynamics and inherited peripheral nerve diseases
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VAP, a versatile access point for the endoplasmic reticulum: review and analysis of FFAT-like motifs in the VAPome
Biochim. Biophys. Acta
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Cleaning house: selective autophagy of organelles
NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes
PIP4K2A regulates intracellular cholesterol transport through modulating PI(4,5)P2 homeostasis
Cholesterol transport through lysosome–peroxisome membrane contacts
L-lactate dehydrogenase A4- and A3B isoforms are bona fide peroxisomal enzymes in rat liver. Evidence for involvement in intraperoxisomal NADH reoxidation
Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites
Mitochondria in peroxisome-deficient hepatocytes exhibit impaired respiration, depleted DNA, and PGC-1α independent proliferation
Biochim. Biophys. Acta
Organelle interplay in peroxisomal disorders
Trends Mol. Med.
Lipid-induced endoplasmic reticulum stress in X-linked adrenoleukodystrophy
Biochim. Biophys. Acta Mol. Basis Dis.
Deficiency of a retinal dystrophy protein, acyl-CoA binding domain-containing 5 (ACBD5), impairs peroxisomal beta-oxidation of very-long-chain fatty acids
MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond
Biochim. Biophys. Acta
The ER–mitochondria tethering complex VAPB–PTPIP51 regulates autophagy
A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis
Am. J. Hum. Genet.
Deciphering the potential involvement of PXMP2 and PEX11B in hydrogen peroxide permeation across the peroxisomal membrane reveals a role for PEX11B in protein sorting
Biochim. Biophys. Acta Biomembr.
Membrane contact sites
Biochim. Biophys. Acta Mol. Cell Res.
A different kind of love – lipid droplet contact sites
Biochim. Biophys. Acta Mol. Cell Biol. Lipids
A tether is a tether is a tether: tethering at membrane contact sites
Mind the organelle gap – peroxisome contact sites in disease
Trends Biochem. Sci.
Metabolic interplaybetween peroxisomes and othersubcellular organelles including mitochondria and the endoplasmic reticulum
Front. Cell Dev. Biol.
Coming together to define membrane contact sites
Organelle interplay – peroxisome interactions in health and disease
J.Inherit. Metab. Dis.
Here, there, and everywhere: the importance of ER membrane contact sites
Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger syndrome ghosts and wild-type peroxisomes
Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes
Nat. Rev. Mol. Cell Biol.
Peroxisome biogenesis, membrane contact sites, and quality control
Biogenesis and function of peroxisomes in human disease with a focus on the ABC transporter
Biol. Pharm. Bull.
Pxmp2 is a channel-forming protein in mammalian peroxisomal membrane
Structure and function of ER membrane contact sites with other organelles
Nat. Rev. Mol. Cell Biol.
A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP
ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43
Applying systems-level spectral imaging and analysis to reveal the organelle interactome
VAPs and ACBD5 tetherperoxisomes to the ER for peroxisome maintenance and lipid homeostasis
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ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER
Peroxisomal ACBD4 interacts with VAPB and promotes ER–peroxisome associations
Cell Cycle Georget. Tex.
ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism
Functional characterisation of peroxisomal β-oxidation disorders in fibroblasts using lipidomics
J.Inherit. Metab. Dis.
Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes
The peroxisome–mitochondria connection: how and why?
Int. J. Mol. Sci.
Intracellular redistribution of neuronal peroxisomes in response to ACBD5 expression
Cholesterol transport through the peroxisome–ER membrane contacts tethered by PI(4,5)P2 and extended synaptotagmins
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© 2019 Elsevier Ltd. All rights reserved.
How do peroxisomes interact with other organelles? ›
Peroxisomes interact with mitochondria in several metabolic path- ways, including b-oxidation of fatty acids and the metabolism of reactive oxygen species. Both organelles are in close contact with the endoplasmic reticulum (ER) and share several proteins, including organelle fission factors.What do peroxisomes interact with? ›
Peroxisomes interact and cooperate with other organelles such as the ER, mitochondria, and lipid droplets to facilitate metabolic processes. Remarkably, they also act as signalling platforms, and contribute to the fine-tuning of cellular processes.How do cell organelles interact with each other? ›
These organelles communicate with one another through vesicular trafficking pathways and membrane contact sites (MCSs). MCSs are sites of close apposition between two or more organelles that play diverse roles in the exchange of metabolites, lipids and proteins.What is the importance of peroxisomes in a cell? ›
Peroxisomes are indispensable for human health and development. They represent ubiquitous subcellular organelles which compartmentalize enzymes responsible for several crucial metabolic processes such as β-oxidation of specific fatty acids, biosynthesis of ether phospholipids and metabolism of reactive oxygen species.How do peroxisomes interact with lysosomes? ›
We further demonstrated that peroxisome forms transient lysosome-peroxisome membrane contact (LPMC) with lysosome through the binding of peroxisomal lipid PI(4,5)P2 by lysosomal protein Synaptotagmin VII (Syt7). Cholesterol can be transported to peroxisome from lysosome through LPMC.How do peroxisomes interact with mitochondria? ›
Among them, mitochondria and peroxisomes interact very closely. They cooperate with each other to maintain lipid balance through fatty acid β-oxidation, to maintain the balance of ROS in cells through scavenging, and to resist foreign invasion through antiviral reactions and other immune responses [87,88,89].How do peroxisomes move around the cell? ›
The canonical view of organelle transport is that organelles directly recruit molecular motors via cargo-specific adaptors. In contrast with this view, we show here that peroxisomes move by hitchhiking on early endosomes, an organelle that directly recruits the transport machinery.What do peroxisomes protect the cell from? ›
Abstract. Peroxisomes are cell organelles that play a central role in lipid metabolism. At the same time, these organelles generate reactive oxygen and nitrogen species as byproducts. Peroxisomes also possess intricate protective mechanisms to counteract oxidative stress and maintain redox balance.What is the main function of peroxisomes quizlet? ›
What is the function of peroxisomes? Peroxisomes contain oxidative enzymes that produce hydrogen peroxide. They also break down fatty acids to Acetyl CoA. PEROXISOMES are small organelles which contain oxidative enzymes.How do peroxisomes and chloroplasts work together? ›
Peroxisomes and chloroplasts share metabolic pathways during photorespiration, supporting efficient photosynthesis.
Do peroxisomes work with mitochondria? ›
Peroxisomes cooperate with mitochondria in the performance of cellular metabolic functions, such as fatty acid oxidation and the maintenance of redox homeostasis. However, whether peroxisomes also regulate mitochondrial fission–fusion dynamics or mitochondrion-dependent apoptosis remained unclear.What is the relationship between Golgi and peroxisomes? ›
Peroxisomes are organelles that contain oxidative enzymes, such as D-amino acid oxidase, urate oxidase, and catalase. They may resemble a lysosome, however, they are not formed in the Golgi complex. Peroxisomes are distinguished by a crystalline structure inside a sac which also contains amorphous gray material.Do peroxisomes break down organelles? ›
Quick look: Peroxisomes, sometimes called microbodies are generally small (about 0.1 – 1.0 µm in diameter) organelles found in animal and plant cells. They can vary in size within the same organism. Peroxisomes break down organic molecules by the process of oxidation to produce hydrogen peroxide.