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

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 Q(10) (CoQ(10)), 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 CoQ(10) 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 H(2)O(2) 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 CoQ(10). It is therefore believed that CoQ(10) prevented the collapse of the mitochondrial membrane potential in response to the H(2)O(2) treatment. Recombinant Bax protein alone caused the ROS generation and release of cytochrome c from isolated mitochondria and, again, CoQ(10) inhibited these Bax-induced mitochondrial dysfunctions.

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

“…Accordingly, we show that Ubisol-Q 10 stabilizes mitochondrial membranes and protects human NT2 and SH-SY5Y cells against apoptotic cell death triggered by either oxidative stress (McCarthy et al, 2004;Somayajulu et al, 2005) or glutamate excitotoxicity (Sandhu et al, 2003). It prevents the release of pro-apoptotic protein Bax as well as cytochrome c from the mitochondria (Naderi et al, 2006). In cybrid cells harboring mitochondrial DNA mutations, Ubisol-Q 10 reduces the generation of ROS and prevents the tertiarybutyl hydroperoxide-induced adenosine triphosphate depletion .…”

Role of Environmental and Inflammatory Toxicity in Neuronal Cell Death

“…Protection of differentiated neuronal cell against cell death induced by glutamate excitotoxicity was also reported by WS-CoQ 10 [135]. Recently, WS-CoQ 10 was shown to inhibit Bax activity and thus prevent Bax-induced destabilization of mitochondria in mammalian cells [136]. Studies in our lab have shown that WSCoQ 10 offers protection against PQ induced neurotoxicity in vivo.…”

Oxidative Stress and Altered Mitochondrial Function in Neurodegenerative Diseases: Lessons From Mouse Models

“…Thus, coenzyme Q (CoQ10) acts a source of O 2 .-when partially reduced (semiquinone form) and as an antioxidant when fully reduced (ubiquinol). Besides its free radical scavenging activity, CoQ10 has been described to prevent apoptotic cell death by blocking Bax binding to mitochondria and by inhibiting activation of the MPT [68,69]. Moreover, CoQ10 is a cofactor of mitochondrial UCPs and therefore, it may also be of benefit through reducing ROS generation via activation of these proteins.…”