Review
Staying in Healthy Contact: How Peroxisomes Interact with Other Cell Organelles

https://doi.org/10.1016/j.molmed.2019.09.012Get rights and content

Highlights

  • In the past decade, studies on MCSs have led to the identification of new MCSs and the molecular constitution of MCSs.

  • Disturbed MCSs between peroxisomes and other cell organelles can cause disease. Such diseases by definition affect several cell organelles and may be termed ‘organelle interaction diseases’.

  • Peroxisome–organelle contact also plays a role in an expanding range of diseases that are not primarily peroxisomal.

  • Advanced understanding of MCSs requires systems-level analysis and opens new horizons to pathomechanisms and interventions.

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 100 nm 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 (Figure 1). 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 close proximity of organelles, typically <30 nm. 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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