Staying in Healthy Contact: How Peroxisomes Interact with Other Cell Organelles (2023)

Table of Contents
Section snippets Peroxisomes: Small Cell Organelles in Need of Contact Peroxisomal Channels and Transporters Peroxisomal Contact Sites Peroxisome–Organelle Interaction Diseases Concluding Remarks Acknowledgments Glossary References (99) Mutant SOD1 mediated pathogenesis of amyotrophic lateral sclerosis Gene Peroxisomal dysfunction in age-related dseases Trends Endocrinol. Metab. Disruption of peroxisome function leads to metabolic stress, mTOR inhibition, and lethality in liver cancer cells Cancer Lett. Peroxisomes and cancer: the role of a metabolic specialist in a disease of aberrant metabolism Biochim. Biophys. Acta Rev. Cancer Peroxisomes are signaling platforms for antiviral innate immunity Cell Genome-wide localization study of yeast Pex11 identifies peroxisome–mitochondria interactions through the ERMES complex J.Mol. Biol. 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. Mitochondrial dynamics and inherited peripheral nerve diseases Neurosci. Lett. VAP, a versatile access point for the endoplasmic reticulum: review and analysis of FFAT-like motifs in the VAPome Biochim. Biophys. Acta Cleaning house: selective autophagy of organelles Dev. Cell NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes J.Biol. Chem. PIP4K2A regulates intracellular cholesterol transport through modulating PI(4,5)P2 homeostasis J.Lipid Res. Cholesterol transport through lysosome–peroxisome membrane contacts Cell L-lactate dehydrogenase A4- and A3B isoforms are bona fide peroxisomal enzymes in rat liver. Evidence for involvement in intraperoxisomal NADH reoxidation J.Biol. Chem. Mitochondrial disruption in peroxisome deficient cells is hepatocyte selective but is not mediated by common hepatic peroxisomal metabolites Mitochondrion 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 J.Biol. Chem. MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond Biochim. Biophys. Acta The ER–mitochondria tethering complex VAPB–PTPIP51 regulates autophagy Curr. Biol. 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 Dev. Cell 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 Nat. Commun. Organelle interplay – peroxisome interactions in health and disease J.Inherit. Metab. Dis. Here, there, and everywhere: the importance of ER membrane contact sites Science Super-resolution imaging reveals the sub-diffraction phenotype of Zellweger syndrome ghosts and wild-type peroxisomes Sci. Rep. Lipid transfer proteins: the lipid commute via shuttles, bridges and tubes Nat. Rev. Mol. Cell Biol. Peroxisome biogenesis, membrane contact sites, and quality control EMBO Rep. 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 PLoS One 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 EMBO J. ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43 Nat. Commun. Applying systems-level spectral imaging and analysis to reveal the organelle interactome Nature VAPs and ACBD5 tetherperoxisomes to the ER for peroxisome maintenance and lipid homeostasis J. Cell Biol. ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER J.Cell Biol. 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 J.Med. Genet. 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 Nature The peroxisome–mitochondria connection: how and why? Int. J. Mol. Sci. Intracellular redistribution of neuronal peroxisomes in response to ACBD5 expression PLoS One Cholesterol transport through the peroxisome–ER membrane contacts tethered by PI(4,5)P2 and extended synaptotagmins Sci. China Life Sci. Cited by (21) C12-HSL is an across-boundary signal molecule that could alleviate fungi Galactomyces's filamentation: A new mechanism on activated sludge bulking ERAD deficiency promotes mitochondrial dysfunction and transcriptional rewiring in human hepatic cells Maintaining social contacts: The physiological relevance of organelle interactions Peroxisome biogenesis and inter-organelle communication: an indispensable role for Pex11 and Pex30 family proteins in yeast Calcium in peroxisomes: An essential messenger in an essential cell organelle Antioxidant Therapy in Cancer: Rationale and Progress Recommended articles (6) Crosstalk between Sertoli and Germ Cells in Male Fertility Organelle communication: Signaling crossroads between homeostasis and disease Balancing the Opposing Principles That Govern Peroxisome Homeostasis Yeast peroxisomes: How are they formed and how do they grow? Brain peroxisomes The ERMES (Endoplasmic Reticulum and Mitochondria Encounter Structures) mediated functions in fungi FAQs Videos

Trends in Molecular Medicine

Volume 26, Issue 2,

February 2020

, Pages 201-214

Author links open overlay panel,

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.

Section snippets

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 [9]), 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 [10], 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

Concluding Remarks

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' [36], 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

Acknowledgments

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.).

Glossary

Demyelination
loss of the myelin sheath along the length of the internode or near the paranodal area. Demyelination results in slow conduction of nerve impulses, causing neurological disease.

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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      2022, Environmental Research

      Fungal bulking is caused by fungi excessive growth and morphological changes, resulting from the evolution toward fungi dominant activated sludge. Communication across fungi and bacteria boundary that mediated by bacterial signal molecules (SMs) probably is the central induce caused fungal bulking occurrence. In this work, it intended to identify the bacterial SM that affected fungal bulking, and verified its roles in regulate the spore germination and hyphal growth. We found C12-HSL concentration decreased significantly from 12.36 to 3.38 ng/g-VSS (P<0.05) when fungal sludge bulking happened, and filamentous Galactomyces's relatively abundant was correlatively enriched. To test the effects of this SM, trace commercial C12-HSL was added to pure cultured Galactomyces, in which spore germination rates decreased by 20% and hyphal extension inhibited by 15%. Ras1-cAMP-PKA and mitogen-activated protein kinase (MAPK) pathways of Galactomyces were responsible for signal C12-HSL transduction, which inhibited peroxisome biosynthesis, suppressed the biological activity of the actin cytoskeleton, and disrupted intercellular organelle transport. All these results showed C12-HSL was the functional SM that could suppress the development of fungal filamentous. This study provided a new insight into the sludge bulking mechanism from view of cross-kingdom communication.

    • ERAD deficiency promotes mitochondrial dysfunction and transcriptional rewiring in human hepatic cells

      2020, Journal of Biological Chemistry

      Mitochondrial dysfunction is associated with a variety of human diseases including neurodegeneration, diabetes, nonalcohol fatty liver disease (NAFLD), and cancer, but its underlying causes are incompletely understood. Using the human hepatic cell line HepG2 as a model, we show here that endoplasmic reticulum-associated degradation (ERAD), an ER protein quality control process, is critically required for mitochondrial function in mammalian cells. Pharmacological inhibition or genetic ablation of key proteins involved in ERAD increased cell death under both basal conditions and in response to proinflammatory cytokines, a situation frequently found in NAFLD. Decreased viability of ERAD-deficient HepG2 cells was traced to impaired mitochondrial functions including reduced ATP production, enhanced reactive oxygen species (ROS) accumulation, and increased mitochondrial outer membrane permeability. Transcriptome profiling revealed widespread down-regulation of genes underpinning mitochondrial functions, and up-regulation of genes associated with tumor growth and aggression. These results highlight a critical role for ERAD in maintaining mitochondrial functional and structural integrity and raise the possibility of improving cellular and organismal mitochondrial function via enhancing cellular ERAD capacity.

    • Maintaining social contacts: The physiological relevance of organelle interactions

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    FAQs

    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.

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    Phone: +2681424145499

    Job: Government Technician

    Hobby: Calligraphy, Lego building, Worldbuilding, Shooting, Bird watching, Shopping, Cooking

    Introduction: My name is Nicola Considine CPA, I am a determined, witty, powerful, brainy, open, smiling, proud person who loves writing and wants to share my knowledge and understanding with you.