title: Mitochondria-targeted antioxidants do not prevent tumour necrosis factor-induced necrosis of L929 cells.
abstract: Mitochondrial production of reactive oxygen species (ROS) is widely reported as a central effector during TNF-induced necrosis. The effect of a family of mitochondria-targeted antioxidants on TNF-induced necrosis of L929 cells was studied. While the commonly used lipid-soluble antioxidant BHA effectively protected cells from TNF-induced necrosis, the mitochondria-targeted antioxidants MitoQ(3), MitoQ(5), MitoQ(10) and MitoPBN had no effect on TNF-induced necrosis. Since BHA also acts as an uncoupler of mitochondrial membrane potential, two additional uncouplers were tested. FCCP and CCCP both provided dose-dependent inhibition of TNF-induced necrosis. In conclusion, the generation of mitochondrial ROS may not be necessary for TNF-induced necrosis. Instead, these results suggest alternative mitochondrial functions, such as a respiration-dependent process, are critical for necrotic death.
authors.affiliation: Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Reagan M
authors.initials: RM
authors.lastname: Jarvis
authors.forename: Jana
authors.initials: J
authors.lastname: Göttert
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Ledgerwood
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D009336:Necrosis / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D002083:Butylated Hydroxyanisole