| Download | - View accepted manuscript: Complexome profiling identifies changes in mitochondrial supercomplexes in murine heart failure (PDF, 1.5 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1152/ajpheart.00278.2025 |
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| Author | Search for: Fong-McMaster, Claire; Search for: McIlroy, Ella; Search for: Levesque, Michelle M.; Search for: Myers, Stephanie; Search for: Pulente, Serena M.; Search for: Gahla, Gurrose; Search for: Lorenzen-Schmidt, Ilka; Search for: Cuperlovic-Culf, Miroslava1ORCID identifier: https://orcid.org/0000-0002-9483-8159; Search for: Haqqani, Arsalan S.2; Search for: Mulvihill, Erin E.ORCID identifier: https://orcid.org/0000-0002-3981-0241; Search for: Harper, Mary-EllenORCID identifier: https://orcid.org/0000-0003-3864-5886 |
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| Affiliation | - National Research Council Canada. Digital Technologies
- National Research Council Canada. Human Health Therapeutics
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| Funder | Search for: University of Ottawa Heart Institute; Search for: Heart and Stroke Foundation of Canada; Search for: Canadian Institutes of Health Research; Search for: Ottawa Institute of Systems Biology-National Research Council |
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| Format | Text, Article |
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| Subject | respirasome; Blue-Native PAGE; oxidative phosphorylation; mass spectrometry; cardiomyopathy |
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| Abstract | Heart failure is characterized by metabolic derangements such as altered substrate metabolism and mitochondrial dysfunction. Mitochondrial supercomplexes, which are higher-order molecular structures comprised of multi-subunit complexes of the electron transport chain, are decreased in heart failure. To investigate the supercomplex proteome composition in heart failure, we used an in vivo myocardial infarction (MI) model in which mice exhibited reduced cardiac function, confirmed by two-dimensional echocardiography at 4 weeks post-infarction. To assess proteins within supercomplexes, we used an emerging technique known as complexome profiling. This technique involved separating out mitochondrial protein complexes using Blue-Native PAGE combined with mass spectrometry to identify proteins within supercomplex gel bands. We identified band-dependent decreases or increases in the relative abundance of subunits of the electron transport chain between MI and sham mice. Decreased abundance of proteins involved in α-ketoglutarate dehydrogenase metabolism including DLST was also identified in the supercomplex bands of MI mice compared to sham mice. In addition, decreased abundance of redox-related proteins such as SOD2 and changes in ribosome protein subunits were identified in the MI mitochondria. In conclusion, we identified changes in the mitochondrial supercomplex proteome in a murine model of heart failure, providing insight and novel mechanisms that may be contributing to the metabolic dysfunction in heart failure. |
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| Publication date | 2025-06-30 |
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| Publisher | American Physiological Society |
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| Licence | |
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| Language | English |
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| In press | Yes |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | e97329a8-f44f-4072-b76f-73017a132105 |
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| Record created | 2025-07-10 |
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| Record modified | 2025-07-10 |
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