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Control of Cardiac Mitochondrial Fuel Selection by Calcium
Author(s) -
Jones Edith,
Van den Bergh Françoise,
Kandel Sunil M.,
Dasika Santosh K.,
Dash Ranjan K.,
Beard Daniel A.
Publication year - 2019
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.2019.33.1_supplement.lb313
Subject(s) - biochemistry , pyruvate dehydrogenase complex , mitochondrion , calcium , isocitrate dehydrogenase , fatty acid , oxidative phosphorylation , citric acid cycle , chemistry , biology , enzyme , organic chemistry
Calcium ion concentration modulates the function of several mitochondrial enzymes. Specifically, the kinetic operations of the decarboxylating dehydrogenases pyruvate dehydrogenase, isocitrate dehydrogenase, alpha‐ketoglutarate dehydrogenase are all affected by [Ca 2+ ]. Previous studies have shown that, despite its ability to affect the function of specific dehydrogenases, [Ca 2+ ] does not substantially alter mitochondrial ATP synthesis in vitro or in vivo in the heart. We hypothesize that, rather than contributing to respiratory control, [Ca 2+ ] plays a role in contributing to fuel selection. Specifically, cardiac mitochondria are able to use different primary carbon substrates (carbohydrates, fatty acids, and ketones) to synthesize ATP aerobically in the living cells. To determine if and how [Ca 2+ ] affects the relative use of carbohydrates versus fatty acids in vitro we measured oxygen consumption and TCA cycle intermediate concentrations in suspensions of cardiac mitochondria with different combinations of pyruvate and palmitoyl‐L‐carnitine in the media at various [Ca 2+ ] and ADP infusion rates. Stoichiometric analysis of the data reveals that when both fatty acid and carbohydrate substrates are available, fuel selection is sensitive to both the rate of ADP infusion and to the calcium concentration. With increasing both the rate of oxidative ATP synthesis and [Ca 2+ ], the fuel utilization ratio shifts to increased fractional consumption of pyruvate. Thus, our results indicate that the effects of ATP synthesis rate and [Ca 2+ ] are interdependent. Support or Funding Information This work supported by NIH grants HL122199 and T32GM008322 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .