Hickey 2014 Abstract MiP2014
|Mitochondrial inefficiencies and anoxic ATP hydrolysis capacities in diabetic rat heart.|
As approximately 80% of diabetics die from heart failure, understanding diabetic cardiomyopathy is crucial. Mitochondria occupy 35-40% of the mammalian cardiomyocyte volume, supply 95% of the hearts’ ATP, and diabetic heart mitochondria show impaired structure, arrangement and function. We predict that bioenergetic inefficiencies are present in diabetic heart mitochondria; therefore, we explored mitochondrial proton and electron handling by linking oxygen flux within streptozotocin (STZ)-induced-diabetic Sprague-Dawley rat heart tissues, to steady-state ATP synthesis, reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨ). By coupling high-resolution respirometers with purpose-built fluorometers, we followed Magnesium Green (ATP synthesis), Amplex Ultra Red (ROS production) and safranin-O (ΔΨ). Relative to control rats, the tissue-mass specific respiration of STZ-diabetic hearts was depressed in oxidative phosphorylating (OXPHOS) states. Steady-state ATP synthesis capacity was almost a third lower in STZ-diabetic heart and relative to O2 flux, this equates to an estimated 12% depression in OXPHOS efficiency. However, with anoxic transition, STZ-diabetic and control heart tissues showed similar ATP hydrolysis capacities through reversal of the F1/F0 ATP synthase. STZ-diabetic cardiac mitochondria also produced more net ROS, relative to oxygen flux (ROS/O) in the OXPHOS state. While ΔΨ did not differ between groups, the time to develop ΔΨ with the onset of OXPHOS was protracted in STZ-diabetic mitochondria. ROS/O is higher in life-like OXPHOS states, and potential delays in the time to develop ΔΨ may delay ATP synthesis with inter-beat fluctuations in ADP concentrations. Whereas diabetic cardiac mitochondria produce less ATP in normoxia, they consume as much ATP in anoxic infarct-like states (Fig. 1).
• O2k-Network Lab: NZ Auckland Hickey AJ
Labels: MiParea: Respiration, mt-Membrane Pathology: Cardiovascular, Diabetes, Myopathy Stress:Ischemia-reperfusion, Oxidative stress;RONS Organism: Rat Tissue;cell: Heart Preparation: Permeabilized tissue
Regulation: ATP production, mt-Membrane potential Coupling state: OXPHOS Pathway: N, S HRR: Oxygraph-2k, O2k-Fluorometer Event: B4, Oral MiP2014
1-School Biol Sc Univ Auckland; 2-Fac Medical Health Sc; 3-Auckland Bioengineering Inst, Univ Auckland; New Zealand. - firstname.lastname@example.org