The permeability transition pore (PTP) is a mitochondrial channel whose opening causes the mitochondrial membrane potential (deltapsi) collapse that leads to apoptosis. Some
ubiquinone analogues have been demonstrated previously to modulate the PTP open-closed transition in isolated mitochondria and thought to act through a common PTP-binding site rather than through oxidation-reduction reactions. We have demonstrated recently both in vitro and in vivo that the ubiquitous
free radical scavenger and respiratory chain
coenzyme Q10 (
CoQ10) prevents keratocyte apoptosis induced by
excimer laser irradiation more efficiently than other
antioxidants. On this basis, we hypothesized that the antiapoptotic property of
CoQ10 could be independent of its
free radical scavenging ability and related to direct inhibition of PTP opening. In this study, we have verified this hypothesis by evaluating the antiapoptotic effects of
CoQ10 in response to apoptotic stimuli, serum
starvation,
antimycin A, and
ceramide, which do not generate
free radicals, in comparison to control,
free radical-generating UVC irradiation. As hypothesized,
CoQ10 dramatically reduced apoptotic cell death, attenuated
ATP decrease, and hindered DNA fragmentation elicited by all apoptotic stimuli. This was accompanied by inhibition of mitochondrial depolarization,
cytochrome c release, and
caspase 9 activation. Because these events are consequent to mitochondrial PTP opening, we suggest that the antiapoptotic activity of
CoQ10 could be related to its ability to prevent this phenomenon.