Coenzyme q10 prevents apoptosis by inhibiting mitochondrial depolarization independently of its free radical scavenging property.

Abstract

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.

• Authors: Laura Papucci, Nicola Schiavone, Ewa Witort, Martino Donnini, Andrea Lapucci, Alessio Tempestini, Lucia Formigli, Sandra Zecchi-Orlandini, Giovanni Orlandini, Giuseppe Carella, Rosario Brancato, Sergio Capaccioli
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 278 Issue 30 Pg. 28220-8 (Jul 25 2003) ISSN: 0021-9258 [Print] United States
• PMID: 12736273 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ceramides
• Coenzymes
• Culture Media, Serum-Free
• Free Radical Scavengers
• Reactive Oxygen Species
• Ubiquinone
• Antimycin A
• Adenosine Triphosphate
• DNA
• Superoxide Dismutase
• Caspase 9
• Caspases
• coenzyme Q10

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antimycin A (pharmacology)
• Apoptosis
• Blotting, Western
• Caspase 9
• Caspases (metabolism)
• Cell Survival
• Ceramides (metabolism, pharmacology)
• Coenzymes
• Culture Media, Serum-Free (pharmacology)
• DNA (metabolism)
• DNA Damage
• DNA Fragmentation
• Free Radical Scavengers (metabolism)
• Keratinocytes (pathology)
• Membrane Potentials
• Microscopy, Fluorescence
• Mitochondria (metabolism)
• Models, Chemical
• Oxidation-Reduction
• Rabbits
• Reactive Oxygen Species
• Superoxide Dismutase (metabolism)
• Time Factors
• Ubiquinone (analogs & derivatives, metabolism, physiology)
• Ultraviolet Rays