Preserved respiratory chain capacity and physiology in mice with profoundly reduced levels of mitochondrial respirasomes
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Abstract
-CIV), that is biochemically and structurally well documented. The role of the respirasome in bioenergetics and the regulation of metabolism is subject to intense debate and is difficult to study because the individual respiratory chain complexes coexist together with high levels of respirasomes. To critically investigate the in vivo role of the respirasome, we generated homozygous knockin mice that have normal levels of respiratory chain complexes but profoundly decreased levels of respirasomes. Surprisingly, the mutant mice are healthy, with preserved respiratory chain capacity and normal exercise performance. Our findings show that high levels of respirasomes are dispensable for maintaining bioenergetics and physiology in mice but raise questions about their alternate functions, such as those relating to the regulation of protein stability and prevention of age-associated protein aggregation.
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Stem cell models of TAFAZZIN deficiency reveal novel tissue-specific pathologies in Barth syndrome
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The mitochondrial protein TMEM177 fine-tunes mammalian cytochrome c oxidase assembly
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Aging and Bioenergetics of Mitochondria
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Mitochondrial cristae remodeling in ischemic stroke: mechanisms and therapeutic perspectives
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- Authors
- Milenkovic, D., Misic, J., Hevler, J. F., Molinié, T., Chung, I., Atanassov, I., Li, X., Filograna, R., Mesaros, A., Mourier, A., Heck, A. J. R., Hirst, J., & Larsson, N.-G.
- Affiliations
- Max Planck Institute for Biology of Ageing (DE)
- Karolinska Institutet (SE)
- Utrecht University (NL)
- Centre National de la Recherche Scientifique (FR)
- University of Cambridge (GB)
- Corresponding author
- Hirst, Judy
- Larsson, Nils-Göran
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-10
- Volume
- 35
- Issue
- 10
- Pages
- 1799-1813.e7
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W4386171179
- Cited by
- 68
- References
- 90
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 23 · 2023: 6
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Funders
- Swedish Cancer Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (SPI.2017.028, 184.034.019)
- Knut och Alice Wallenbergs Stiftelse (2019.0109, 2016.0050)
- Max-Planck-Gesellschaft
- Novo Nordisk
- Vetenskapsrådet (2015-00418)
- Novo Nordisk Fonden (NNF22OC0078444, NNF20OC0063616, NNF20OC006316)
- Medical Research Council (MC_UU_00015/2, MC_U105663141, MC_UU_00015/7)
- H2020 European Research Council (741366)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- respirasome, electron transport chain, cytochrome c oxidase, mitochondrial bioenergetics, knock-in mice, exercise performance, protein stability, protein aggregation
- MeSH terms
- Animals, Electron Transport Complex IV, Electron Transport, Energy Metabolism, Mammals, Mitochondria, Mitochondrial Membranes, Mice
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