Journal article
Impaired utilization of membrane potential by complex II-energized mitochondria of obese, diabetic mice assessed using ADP recycling methodology
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.311(4), pp.R756-R763
10/01/2016
DOI: 10.1152/ajpregu.00232.2016
PMID: 27558314
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 O-2 flux vs. [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 O-2 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 Delta psi and that more ADP is required for peak O-2 flux.
Details
- Title: Subtitle
- Impaired utilization of membrane potential by complex II-energized mitochondria of obese, diabetic mice assessed using ADP recycling methodology
- Creators
- Brian D. Fink - University of IowaFan Bai - University of IowaLiping Yu - University of IowaWilliam I. Sivitz - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.311(4), pp.R756-R763
- Publisher
- Amer Physiological Soc
- DOI
- 10.1152/ajpregu.00232.2016
- PMID
- 27558314
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Number of pages
- 8
- Grant note
- Iowa Affiliate Fraternal Order of the Eagles 5I01BX000285-06 / Merit Review Award from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service I01BX000285 / Veterans Affairs; US Department of Veterans Affairs
- Language
- English
- Date published
- 10/01/2016
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Medicine Administration; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984627331102771
Metrics
2 Record Views