Fink 2016 Am J Physiol Regul Integr Comp Physiol

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Fink BD, Bai F, Yu L, Sivitz WI (2016) Impaired utilization of membrane potential by complex II-energized mitochondria of obese, diabetic mice assessed using ADP recycling methodology. Am J Physiol Regul Integr Comp Physiol 311:756-63.

» PMID: 27558314

Fink BD, Bai F, Yu L, Sivitz WI (2016) Am J Physiol Regul Integr Comp Physiol

Abstract: Recently, we used an ADP recycling approach to examine mouse skeletal muscle (SkM) mitochondrial function over respiratory states intermittent between state 3 and 4. We showed that respiration energized at complex II by succinate, in the presence of rotenone to block complex I, progressively increased with incremental additions of ADP. However, in the absence of rotenone, respiration peaked at low [ADP] but then dropped markedly as [ADP] was further increased. Here, we tested the hypothesis that these respiratory dynamics would differ between mitochondria of mice fed high-fat (HF) and treated with a low dose of streptozotocin to mimic type 2 diabetes and mitochondria from controls. We found that respiration and ATP production on succinate alone for both control and diabetic mice increased to a maximum at low [ADP] but dropped markedly as [ADP] was incrementally increased. However, peak respiration by the diabetic mitochondria required a higher [ADP] (right shift in the curve of O2 flux verses [ADP]). ATP production by diabetic mitochondria respiring on succinate alone was significantly less than controls whereas membrane potential trended higher, indicating that utilization of potential for oxidative phosphorylation was impaired. The rightward shift in the curve of O2 flux versus [ADP] is likely a consequence of these changes in ATP production and potential. In summary, using an ADP recycling approach, we demonstrated that ATP production by SkM mitochondria of HF/streptozotocin diabetic mice energized by succinate is impaired due to decreased utilization of ΔΨ and that more ADP is required for peak O2 flux.

Copyright © 2016, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

Keywords: Bioenergetics, Diabetes, Mitochondria, Obesity, Succinate

O2k-Network Lab: US IA Iowa City Sivitz WI

Labels: MiParea: Respiration, mt-Membrane, Exercise physiology;nutrition;life style  Pathology: Diabetes, Obesity 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 

Regulation: ADP, ATP production  Coupling state: LEAK, OXPHOS  Pathway:HRR: Oxygraph-2k, TPP