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Calcium Regulation of Mitochondrial Respiration is Substrate Dependent and Tissue Specific
Author(s) -
Kandel Sunil M,
Tomar Namrata,
Audi Said H,
Camara Amadou K S,
Cowley Allen W,
Dash Ranjan K
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb170
Subject(s) - mitochondrion , pyruvate dehydrogenase complex , stimulation , biochemistry , respiration , respiratory system , calcium , dehydrogenase , biology , kidney , citric acid cycle , respiratory chain , enzyme , chemistry , endocrinology , anatomy , organic chemistry
Mitochondrial Krebs cycle dehydrogenase enzymes, such as pyruvate dehydrogenase, isocitrate dehydrogenase, and alpha‐ketoglutarate dehydrogenase, have been shown to be stimulated by calcium ion concentration, [Ca 2+ ], in isolated enzyme experimental systems. However, the extents of the [Ca 2+ ] stimulation of these enzymes and the resulting integrated stimulatory effects on mitochondrial energy metabolism (ATP synthesis) in situ or in vivo in the heart and other tissue/organ systems, such as kidney, is controversial and/or not yet well‐understood. This may be due to several compounding factors, such as the use of specific respiratory substrates in isolated mitochondrial experimental system to energize the mitochondria, and/or the way the mitochondrial [Ca 2+ ] is perturbed. In this study, we hypothesize that the extents of the [Ca 2+ ] stimulation is critically dependent on the specific choice of the respiratory substrates and the modes of mitochondrial [Ca 2+ ] perturbations, and that this substrate‐dependent [Ca 2+ ] stimulation is also tissue specific. Consequently, alterations in the respiratory substrates can lead to dramatically different respiratory rates in isolated mitochondria from the heart and kidney. To test this hypothesis, we used isolated mitochondria from two different organs (i.e. heart and kidney) from Sprague‐Dawley rats and measured oxygen consumption rates in different respiratory states: leak state (energized mitochondria in the absence of ADP) and ADPstimulated state (energized mitochondria in the presence of saturating concentrations of ADP) with/without bolus injections of different concentrations of CaCl 2 using an Oroboros Oxygraph‐ 2k Instrument in the presence of a variety of respiratory substrates, including pyruvate + malate (PM), glutamate + malate (GM), alpha‐ketoglutarate + malate (AM), palmitoyl‐L‐carnitine + malate (PCM), and succinate (SUC). We found that CaCl 2 at a certain range of concentrations differentially enhance the mitochondrial respiration (ATP synthesis) when the isolated mitochondria was fed with different respiratory substrates and their response was tissue dependent. Calcium significantly increased the mitochondrial state III respiration with GM and AM substrates compared to PM substrate in both organs, but the calcium effect on the mitochondrial respiration was more prominent in the kidney compare to the heart. These results suggest that the energized isolated mitochondria in the presence of calcium do not respond the same when the different substrates are used and the effective energy metabolism and the production of ATP may require a suitable substrate combination to be comparable to in vivo condition. Support or Funding Information NIH grants P01‐GM066730, U01‐HL122199 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .