Journal article
Regulation of ATP production: dependence on calcium concentration and respiratory state
American Journal of Physiology: Cell Physiology, Vol.313(2), pp.C146-C153
08/01/2017
DOI: 10.1152/ajpcell.00086.2017
PMID: 28515085
Abstract
Nanomolar free calcium enhances oxidative phosphorylation. However, the effects over a broad concentration range, at different respiratory states, or on specific energy substrates are less clear. We examined the action of varying [Ca
] over respiratory states ranging 4 to 3 on skeletal muscle mitochondrial respiration, potential, ATP production, and H
O
production using ADP recycling to clamp external [ADP]. Calcium at 450 nM enhanced respiration in mitochondria energized by the complex I substrates, glutamate/malate (but not succinate), at [ADP] of 4-256 µM, but more substantially at intermediate respiratory states and not at all at state 4. Using varied [Ca
], we found that the stimulatory effects on respiration and ATP production were most prominent at nanomolar concentrations, but inhibitory at 10 µM or higher. ATP production decreased more than respiration at 10 µM calcium. However, potential continued to increase up to 10 µM; suggesting a calcium-induced inability to utilize potential for phosphorylation independent of opening of the mitochondrial permeability transition pore (MTP). This effect of 10 µM calcium was confirmed by direct determination of ATP production over a range of potential created by differing substrate concentrations. Consistent with past reports, nanomolar [Ca
] had a stimulatory effect on utilization of potential for phosphorylation. Increasing [Ca
] was positively and continuously associated with H
O
production. In summary, the stimulatory effect of calcium on mitochondrial function is substrate dependent and most prominent over intermediate respiratory states. Calcium stimulates or inhibits utilization of potential for phosphorylation dependent on concentration with inhibition at higher concentration independent of MTP opening.
Details
- Title: Subtitle
- Regulation of ATP production: dependence on calcium concentration and respiratory state
- 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: Cell Physiology, Vol.313(2), pp.C146-C153
- DOI
- 10.1152/ajpcell.00086.2017
- PMID
- 28515085
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 08/01/2017
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Medicine Administration; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984627330502771
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