Wuest 2017 Abstract MITOEAGLE Barcelona
Mitochondrial Complex I function in heart failure: different angles to analyze mitochondrial function.
Wuest RCI (2017)
Event: MitoEAGLE Barcelona 2017
In cardiac hypertrophy (CH) and heart failure (HF), alterations occur in mitochondrial enzyme content and activities but the origin and implications of these changes for mitochondrial function need to be resolved.
Right ventricular CH or HF was induced by monocrotaline injection, which causes pulmonary artery hypertension, in rats. Results were compared with saline injection (CON). NAD(P)H and FAD autofluorescence were recorded in thin intact cardiac trabeculae during transitions in stimulation frequency, to assess mitochondrial Complex I and Complex II function, respectively. Mitochondrial oxygen consumption, morphology, protein content, and enzymatic activity were assessed. NAD(P)H autofluorescence upon an increase in stimulation frequency showed a rapid decline followed by a slow recovery. The amplitude of the early rapid change in NAD(P)H autofluorescence was severely depressed in CH and HF compared with CON, but to a lesser extent for FAD in CH and HF. Complex I-coupled respiration showed a ∼3.5-fold reduction in CH and HF; Complex II-coupled respiration was depressed two-fold in HF. Protein content of Complex I subunits and isolated Complex I activity in supercomplexes were modestly reduced in CH and HF. Mitochondrial volume density was similar, but remodeling was evident from changes in ultrastructure and fusion/fission indices in CH and HF . Complex I dysfunction is observed in CH and HF, although it remains to be determined whether this is a cause or consequence of mitochondrial remodeling. Future work is directed to identify compounds that alter mitochondrial bio-energetic function in cardiac myocytes, using Oroboros Oxygraph-2k and Seahorse XF technology.
Labels: MiParea: Respiration, mt-Structure;fission;fusion Pathology: Cardiovascular
Organism: Rat Tissue;cell: Heart
Pathway: N, S HRR: Oxygraph-2k Event: A2
- Lab Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands. – [email protected]
- Wuest RCI, de Vries HJ, Wintjes LT, Rodenburg RJ, Niessen HW, Stienen GJ (2016) Mitochondrial Complex I dysfunction and altered NAD(P)H kinetics in rat myocardium in cardiac right ventricular hypertrophy and failure. Cardiovasc Res 111:362-72.