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Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells

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Abstract

Oxidative stress leads to mitochondrial dysfunction, which triggers the opening of the permeability transition pores (PTP) and the release of pro-apoptotic factors causing apoptotic cell death. In a limited number of cell systems, anti-oxidants and free-radical scavengers have been shown to block this response. We have previously reported that coenzyme Q10 (CoQ10), an electron carrier in the mitochondrial respiratory chain, is involved in the reactive oxygen species (ROS) removal and prevention of oxidative stress-induced apoptosis in neuronal cells. However, the mechanism of this protection has not been fully elucidated. In the present study we investigated the effects of CoQ10 on the mitochondrial events characteristic to apoptosis, especially on the function of pro-apoptotic protein Bax. Our results demonstrated that following a brief exposure of two human cell lines (fibroblasts and HEK293 cells) to H2O2 the intracellular levels of ROS and the association of Bax with the mitochondria significantly increased and the cells underwent apoptosis. Both of these events, as well as the release of cytochrome c from the mitochondria, were blocked by a 24 h pre-treatment with CoQ10. It is therefore believed that CoQ10 prevented the collapse of the mitochondrial membrane potential in response to the H2O2 treatment. Recombinant Bax protein alone caused the ROS generation and release of cytochrome c from isolated mitochondria and, again, CoQ10 inhibited these Bax-induced mitochondrial dysfunctions.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada, N9B 3P4

    Jafar Naderi, Mallika Somayajulu-Nitu, Amit Mukerji, Priya Sharda & Siyaram Pandey

  2. Institute for Biological Sciences, National Research Council of Canada, 1200 Montreal Road, Bldg. M-54, Ottawa, ON, K1A 0R6

    Marianna Sikorska & Henryk Borowy-Borowski

  3. Serono Pharmaceutical Research Institute, 14 chemin des Aulx, 1228, Plan-les-Ouates, Geneva, Switzerland

    Bruno Antonsson

Authors
  1. Jafar Naderi
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  2. Mallika Somayajulu-Nitu
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  3. Amit Mukerji
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  4. Priya Sharda
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  5. Marianna Sikorska
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  6. Henryk Borowy-Borowski
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  7. Bruno Antonsson
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  8. Siyaram Pandey
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Correspondence to Siyaram Pandey.

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Naderi, J., Somayajulu-Nitu, M., Mukerji, A. et al. Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells. Apoptosis 11, 1359–1369 (2006). https://doi.org/10.1007/s10495-006-8417-4

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  • DOI: https://doi.org/10.1007/s10495-006-8417-4

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