BNIP3 regulates cardiac energy metabolism by interaction with F1FO ATP-synthase

Abstract Background The oxidative phosphorylation (OXPHOS) that takes place in the mitochondria produces chemical energy form of ATP, main source heart. Proper mitochondrial function determines contractility Changes myocardial ATP levels are often associated with cardiovascular disease. However, dysfunction remains an unmet therapeutic challenge. F1FO ATP-synthase protein complex catalyses last step OXPHOS, synthesising and determining respiratory cardiac mitochondria. An increased pool during challenges, regulated by ATP-synthase, could therefore significantly improve clinical outcome affected patients. In neurons, Bcl2-familiy members like BCL2/adenovirus E1B 19 kDa protein-interacting 3 (BNIP3) have been suggested to be involved regulation metabolic efficiency through interaction synthase. A similar context unclear. Furthermore, BNIP3 has a significant impact on loss cardiomyocytes under various pathological conditions is thus potential mediator metabolism cardiomyocytes. Methods results With native gel-electrophoresis, C57BL/6J mice was first identified higher oligomeric complexes molecular weight range as ATP-synthase. Using 60Å-precise proximity-ligation assays determine possible binding partners, uncovered for time interacting BNIP3. This confirmed co-immunoprecipitation spatial localization using electron microscopy. Peptide microarray studies elucidate f subunit structural site. Functional analysis extracellular flux analyser technology revealed elevated activity Bnip3 knock out human inhibition. Increased after acute inhibition observed regulatory effect activity. Finally, depletion improves stress resistance augmented chronotropic capacity dobutamine-induced stress. Conclusion Depletion suggests role homeostasis via F1F0 complexes. Since allows positive modulation performance elevating available pool, this may serve beneficial treatment patients disease future. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): German research foundation (DFG)