Peroxisomes are juxtaposed to strategic sites on mitochondria
Abstract
Peroxisomes are ubiquitous and dynamic organelles that house many important pathways of cellular metabolism. In recent years it has been demonstrated that mitochondria are tightly connected with peroxisomes and are defective in several peroxisomal diseases. Indeed, these two organelles share metabolic routes as well as resident proteins and, at least in mammals, are connected via a vesicular transport pathway. However the exact extent of cross-talk between peroxisomes and mitochondria remains unclear. Here we used a combination of high throughput genetic manipulations of yeast libraries alongside high content screens to systematically unravel proteins that affect the transport of peroxisomal proteins and peroxisome biogenesis. Follow up work on the effector proteins that were identified revealed that peroxisomes are not randomly distributed in cells but are rather localized to specific mitochondrial subdomains such as mitochondria-ER junctions and sites of acetyl-CoA synthesis. Our approach highlights the intricate geography of the cell and suggests an additional layer of organization as a possible way to enable efficient metabolism. Our findings pave the way for further studying the machinery aligning mitochondria and peroxisomes, the role of the juxtaposition, as well as its regulation during various metabolic conditions. More broadly, the approaches used here can be easily applied to study any organelle of choice, facilitating the discovery of new aspects in cell biology.
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MDM34 encodes a protein of the mitochondrial outer membrane that is part of the ERMES complex, which tethers mitochondria to the ER and is also involved in their contact with peroxisomes.
“MDM34 encodes a protein of the mitochondrial outer membrane that is a part of the ERMES complex that tethers mitochondria to the ER and is also involved in their contact with peroxisomes (Kornmann et al. 2009; Cohen et al. 2014).”
From Mitochondrial retrograde control of transcription evolves with respiratory stress, metabolic adaptation, and virulence in budding yeasts (2026) · cites this paper as Cohen et al. 2014
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The Peroxisome-Mitochondria Connection: How and Why?
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“In yeast, it has been shown that peroxisomes preferentially localize to specific mitochondrial subdomains such as mitochondria-associated ER membranes (MAMs) and sites of acetyl-CoA synthesis [68], and that these peroxisome-mitochondria contact sites are established by direct interaction between Pex11, a peroxisomal m…”
BackgroundShai, N., Yifrach, E., van Roermund, C. W. T., Cohen, N., Bibi, C., IJlst, L., Cavellini, L., Meurisse, J., Schuster, R., Zada, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-03957-8 · Cited by 320 · see citing works
Self-citationOrganelle interplay-peroxisome interactions in health and disease.
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Łabędzka-Dmoch, K., Bui, T. H. D., Piątkowski, J., Dilling, M., Jagiełło, P., Kabza, W., & Golik, P. (2026) · Molecular Biology and Evolution · doi:10.1093/molbev/msag005 · Cited by 1 · see citing works
- Authors
- Cohen, Y., Klug, Y. A., Dimitrov, L., Erez, Z., Chuartzman, S. G., Elinger, D., Yofe, I., Soliman, K., Gärtner, J., Thoms, S., Schekman, R., Elbaz-Alon, Y., Zalckvar, E., & Schuldiner, M.
- Affiliations
- Weizmann Institute of Science (IL)
- University of California System (US)
- Universitätsmedizin Göttingen (DE)
- Department of Molecular Genetics, Weizmann Institute of Science a , Rehovot 7610001, Israel yael.elbaz@weizmann.ac.il einat.zalckvar@weizmann.ac.il maya.schuldiner@weizmann.ac.il
- Corresponding author
- Zalckvar, Einat
- Schuldiner, Maya
- ORCID
- Venue
- Molecular BioSystems
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-03-25
- Volume
- 10
- Issue
- 7
- Pages
- 1742-1748
- ISSN
- 1742-2051 (ISSN-L)
- 1742-206X
- OpenAlex
- W2061764676
- Cited by
- 117
- References
- 32
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 11 · 2021: 5 · 2020: 12 · 2019: 10 · 2018: 15 · 2017: 11 · 2016: 11 · 2015: 11 · 2014: 2
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular BioSystems (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Research Council (StG 260395)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- peroxisomes, mitochondria, peroxisome biogenesis, acetyl-CoA biosynthesis, peroxisomal disorders, organelle localization, yeast genetic screen, high-content screening
- MeSH terms
- Acetyl Coenzyme A, Endoplasmic Reticulum, Mitochondria, Saccharomyces cerevisiae, Mutagenesis, Peroxisomes, Protein Transport, Saccharomyces cerevisiae Proteins
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