Mammalian electron transfer flavoproteins comprise a mitochondrial matrix heterodimer, and an electron transfer flavoprotein dehydrogenase localized in the mitochondrial inner membrane. Electrons from primary acyl-CoA dehydrogenases, of mitochondrial metabolism of fatty acids and amino acids, are transferred to the matricial heterodimer and, subsequently, to the electron transfer flavoprotein dehydrogenase, which transfers electrons to ubiquinone of the mitochondrial electron transport chain. Several evidences suggest that these proteins may convey electrons directly to molecular oxygen, yielding reactive oxygen species. In this work, we investigated phenotypes of the yeast mutants affected in the orthologous genes of the matrix heterodimer (AIM45 and YGR207c/CIR1) and of the electron transfer flavoprotein dehydrogenase (YOR356w/CIR2). The mutant strains aim45 and yor356w/cir2 displayed better growth on several non-fermentable carbon sources, which depended on the component of the electron transport chain that accepts the electrons resulting from its mitochondrial oxidation. Furthermore, upon heat shock, the mutant strains presented decreased intracellular oxidation, suggesting that these flavoproteins are a source of reactive oxygen species. Other phenotypes identified suggest that AIM45, YGR207c/CIR1 and YOR356w/CIR2 can protect cells from oxidative and heat stress, which encompass increased heat stress sensitivity, superoxide sensitivity, both only on non-fermentable carbon sources.

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BackgroundThe lack of cardiac β1-adrenergic receptors (β1-AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF.ObjectiveWe tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β1 adrenergic receptor knockout (β1ARKO) mice.MethodsFour- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons.ResultsThe β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β1ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β1ARKO mice.ConclusionMCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.