Complex I Deficiency Due to Selective Loss of Ndufs4 in the Mouse Heart Results in Severe Hypertrophic Cardiomyopathy
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No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
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all 1,000 screened works →All three models called this out of scope.
Mouse genetic model of complex I deficiency and cardiomyopathy.
The study investigates mitochondrial dysfunction and cardiomyopathy in mice.
Mouse model of cardiac complex I deficiency; biomedical pathophysiology.
Abstract
Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼ 50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.
Stored with the screening record, where it is evidence for the labels above.
The record
- Venue
- PLoS ONE
- Topic
- Mitochondrial Function and Pathology
- Field
- Biochemistry, Genetics and Molecular Biology
- Canadian institutions
- —
- Funders
- ServierCanadian Institutes of Health ResearchGates Cambridge TrustMedical Research CouncilCambridge TrustBritish Heart Foundation
- Keywords
- Hypertrophic cardiomyopathyMitochondrionCardiomyopathyInternal medicineOxidative phosphorylationMitochondrial respiratory chainFibrosisReactive oxygen speciesEndocrinologyHeart failureBiologyMedicineCardiologyCell biologyBiochemistry
- Has abstract in OpenAlex
- yes