Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection

Generation of free radicals is often associated with the induction and prog ression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and can help to elucidate specific apoptotic pathways. Here we studied whether coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiqu inone) forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells to alpha -tocopheryl succinate (alpha -TOS), hydrogen peroxide , anti-Fas IgM or TRAIL led to induction of apoptosis. Cell death due to th e chemical agents was suppressed in cells enriched with the reduced form of coenzyme Q. However, coenzyme Q did not block cell death induced by the im munological agents. Ubiquinol-10 inhibited reactive oxygen species (ROS) ge neration in cells exposed to alpha -TOS, and a mitochondrially targeted coe nzyme Q analogue also blocked apoptosis triggered by alpha -TOS or hydrogen peroxide. Therefore, it is plausible that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as an antioxidant in mitochondria. Our results also indicate that generation of free radicals may not be a cri tical step in induction of apoptosis by immunological agents. (C) 2001 Fede ration of European Biochemical Societies. Published by Elsevier Science B.V . All rights reserved.