Antioxidants reduce peroxyl-mediated inhibition of mitochondrial transcription.

We have recently shown that the mitochondrial transcription system is extremely sensitive to inhibition by peroxyl radicals generated by either 2,2'-azobis(2-amidinopropane) (AAPH) or 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN), and that this inhibition occurs prior to detectable evidence of lipid peroxidation as measured by thiobarbituric acid (TBA)-reactive substances, 4-hydroxynonenal accumulation, and oxygen consumption. In this report, we further confirm that mitochondrial transcription is sensitive to oxidative stress. We also demonstrate that alpha-tocopherol, ascorbate, and glutathione can partially attenuate these effects, but none of the three, nor the three together, are capable of completely preventing this oxidant-induced repression. This suggests that these physiological antioxidants, while capable of preventing lipid peroxidation chain reactions, are less effective at protecting the mitochondrial transcriptional machinery against this oxidative insult.