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Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF.

1993; Springer Nature; Volume: 12; Issue: 8 Linguagem: Inglês

10.1002/j.1460-2075.1993.tb05978.x

1460-2075

Klaus Schulze‐Osthoff, Rudi Beyaert, Veronique Vandevoorde, Guy Haegeman, Walter Fiers,

RNA modifications and cancer

Research Article1 August 1993free access Depletion of the mitochondrial electron transport abrogates the cytotoxic and gene-inductive effects of TNF. K. Schulze-Osthoff K. Schulze-Osthoff Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author R. Beyaert R. Beyaert Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author V. Vandevoorde V. Vandevoorde Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author G. Haegeman G. Haegeman Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author W. Fiers W. Fiers Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author K. Schulze-Osthoff K. Schulze-Osthoff Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author R. Beyaert R. Beyaert Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author V. Vandevoorde V. Vandevoorde Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author G. Haegeman G. Haegeman Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author W. Fiers W. Fiers Laboratory of Molecular Biology, University of Ghent, Belgium. Search for more papers by this author Author Information K. Schulze-Osthoff1, R. Beyaert1, V. Vandevoorde1, G. Haegeman1 and W. Fiers1 1Laboratory of Molecular Biology, University of Ghent, Belgium. The EMBO Journal (1993)12:3095-3104https://doi.org/10.1002/j.1460-2075.1993.tb05978.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Tumor necrosis factor (TNF) has cytotoxic and gene-inductive activities on several cell types. Previous studies on L929 fibrosarcoma cells have revealed that the mitochondrial electron transport system plays a key role in inducing TNF cytotoxicity, presumably by the formation of reactive oxygen intermediates (ROI). Here we report that mitochondria-derived intermediates are not only cytotoxic but, in addition, function as signal transducers of TNF-induced gene expression. The activation of NF kappa B, which fulfills an important role in TNF-induced gene transcription, could be blocked by interference with the mitochondrial electron transport system. Furthermore, antimycin A, a mitochondrial inhibitor that increases the generation of ROI, potentiated TNF-triggered NF kappa B activation. The dual role of mitochondria-derived intermediates in cytotoxicity and immediate-early gene induction of TNF was further substantiated by isolating L929 subclones which lacked a functional respiratory chain. This depletion of the mitochondrial oxidative metabolism resulted in resistance towards TNF cytotoxicity, as well as in inhibition of NF kappa B activation and interleukin-6 gene induction by TNF. These findings suggest that mitochondria are the source of second messenger molecules and serve as common mediators of the TNF-cytotoxic and gene-regulatory signaling pathways. Previous ArticleNext Article Volume 12Issue 81 August 1993In this issue RelatedDetailsLoading ...