Trends in Molecular Medicine
ReviewStaying in Healthy Contact: How Peroxisomes Interact with Other Cell Organelles
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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2022, Environmental ResearchCitation Excerpt :Specifically, the genes in peroxisomes, responsible for importing matrix proteins, were significantly down-regulated. Pex5, a shuttling receptor for PTS1 proteins, and the recycling enzymes Pex1 and Pex6 that depend on ATP-dependent export (Sargsyan and Thoms, 2019), were above 1-fold down regulated. The down-regulation of PEX2 suggested that the endoplasmic reticulum and mitochondria were suppressed (See Fig. 7b).
ERAD deficiency promotes mitochondrial dysfunction and transcriptional rewiring in human hepatic cells
2020, Journal of Biological ChemistryCitation Excerpt :Given the essential roles of mitochondria in regulating cellular physiology, metabolism, and cell death (20), our results suggest that mitochondrial dysfunction may be an under-appreciated driver of many ER stress-induced pathogenesis. These results also strongly support an increasingly recognized notion that normal cellular and organismal health depends on tightly regulated inter-organelle interaction and communication, particularly under stressed conditions, such as viral infection or obesity (21). Our results provide some mechanistic evidence to explain how ERAD deficiency leads to mitochondrial dysfunction.
Maintaining social contacts: The physiological relevance of organelle interactions
2020, Biochimica et Biophysica Acta - Molecular Cell ResearchCitation Excerpt :Current research is now focusing on the regulation of MCSs and their physiological functions, and it is becoming evident that MCSs are central to cell physiology and impact on human health and disease, thus changing our current understanding of disease pathology [13–19]. The ER has long been the focus of MCS research [4,20–22], but MCS between other subcellular organelles have also been discovered, including mitochondria, peroxisomes, lipid droplets and lysosomes [23–27]. In this review, we will provide a comprehensive overview of the physiological relevance of organelle contacts.
Tissue-specific roles of peroxisomes revealed by expression meta-analysis
2024, Biology DirectGluing yeast peroxisomes – composition and function of membrane contact sites
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