The two faces of a same function: pro- and antiapoptotic role of ubiquinone

Abstract

Ubiquinone or coenzyme Q is an essential lipid present in almost all the cell membranes. It is a redox molecule able to accept and donate electrons to several other cellular components. This redox capability is key in the two main functions of ubiquinone in cells, an intermediate in the mitochondrial respiratory chain and the main lipidic antioxidant in cell membranes. During the last years, several works have confirmed the essential role of ubiquinone in life and death of cells. Several evidences indicate that ubiquinone is involved in cell defence against oxidative damage of membranes and particularly plasma membrane. Serum withdrawal increases lipid hydroperoxide levels resulting in a neutral sphingomyelinase-mediated apoptosis. Ubiquinone inhibits neutral sphingomyelinase activation preventing ceramide-dependen apoptosis. The cell population is based on the equilibrium between proliferation and cell death. The activation of cell growth factors leads to an increase of proliferation by activation of transduction signals, which activate/repress transcription factors involved on regulation of either anti- or pro-apoptotic genes. Multiple forms of tumor exhibit abnormal constitutive activation of phosphatidylinositol 3-kinase/Akt pathway, which is activated by several growth factors and constitutes a mechanism of tumor cells survival. Current evidence in our group support that biosynthesis of ubiquinone can be regulated by survival signal such as Akt or inhibitor kappa-B kinase path ways through of Nuclear Factor kappa-B and/or Forkhead Box Class O, a critical factor in the regulation of cell cycle arrest, apoptosis, and resistance to oxidate stress. Recent research has demonstrated that cells respond to chemotherapic agents by increasing ubiquinone levels, probably in an attempt of protect themselves from reactive oxygen species production. In addition, ubiquinone seems to be an important agent in the prevention of cell damage during aging as suggested by its increase in plasma membrane of caloric restricted animals. However, mitochondrial reduced and semireduced ubiquinone species are also a source of oxygen radicals that could promote molecular damage and apoptosis. Also, the insertion of foreign forms of ubiquinone to mitochondrial membranes induces higher levels of reactive oxygen species in cells and tissues. We show here a wide review of the two faces of a same function, the transfer of electrons by ubiquinone. Pro- and antiapoptotic cell mechanisms are dependent on this essential lipidic factor.