Impaired mitochondrial Ca{sup 2+} homeostasis in respiratory chain-deficient cells but efficient compensation of energetic disadvantage by enhanced anaerobic glycolysis due to low ATP steady state levels
- Institute of Vegetative Physiology, University of Koeln, Robert-Koch-Str. 39, 50931 Cologne (Germany)
- Department of Preclinical, Clinical Pharmacology and Biochemistry, University of Medicine Varna, 55 Marin Drinov Str. 9002, 9002 Varna (Bulgaria)
- Institute for Clinical Chemistry, University of Koeln, Kerpener Str. 62, 50924 Cologne (Germany)
- Institute of Naturopathy, University of Koeln, Joseph-Stelzmann-Str. 9, 50924 Cologne (Germany)
- Institute of Experimental Medicine, University of Koeln, Robert-Koch-Str. 10, 50931 Cologne (Germany)
Energy-producing pathways, adenine nucleotide levels, oxidative stress response and Ca{sup 2+} homeostasis were investigated in cybrid cells incorporating two pathogenic mitochondrial DNA point mutations, 3243A > G and 3302A > G in tRNA{sup Leu(UUR)}, as well as Rho{sup 0} cells and compared to their parental 143B osteosarcoma cell line. All cells suffering from a severe respiratory chain deficiency were able to proliferate as fast as controls. The major defect in oxidative phosphorylation was efficiently compensated by a rise in anaerobic glycolysis, so that the total ATP production rate was preserved. This enhancement of glycolysis was enabled by a considerable decrease of cellular total adenine nucleotide pools and a concomitant shift in the AMP + ADP/ATP ratios, while the energy charge potential was still in the normal range. Further important consequences were an increased production of superoxide which, however, was neither escorted by major changes in the antioxidative defence systems nor was it leading to substantial oxidative damage. Most interestingly, the lowered mitochondrial membrane potential led to a disturbed intramitochondrial calcium homeostasis, which most likely is a major pathomechanism in mitochondrial diseases.
- OSTI ID:
- 20972103
- Journal Information:
- Experimental Cell Research, Vol. 313, Issue 14; Other Information: DOI: 10.1016/j.yexcr.2007.04.015; PII: S0014-4827(07)00165-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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