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Tumor necrosis factor is delivered to mitochondria where a tumor necrosis factor-binding protein is localized.
- Source :
-
Laboratory investigation; a journal of technical methods and pathology [Lab Invest] 1998 Dec; Vol. 78 (12), pp. 1583-9. - Publication Year :
- 1998
-
Abstract
- The roles of the known tumor necrosis factor (TNF) receptors (TNFR-I and TNFR-II) and their associated signaling pathways in mediating the diverse actions of TNF remain incompletely defined. We have found that a proportion of exogenous TNF is delivered to mitochondria as well as to lysosomes. Using confocal and immunoelectron microscopy and Western blotting of subcellular fractions, we have identified a 60-kd protein in the inner mitochondrial membrane that is recognized by a monoclonal antibody to TNFR-II. In isolated mitochondria, this protein binds [125I]-TNF. This provides evidence of a mitochondrial binding protein for an extracellular ligand and demonstrates the presence of a pathway capable of delivering TNF from the cell surface to mitochondria. These findings suggest that TNF effects on cells may be due in part to a direct effect on mitochondria.
- Subjects :
- Adipocytes cytology
Adipocytes ultrastructure
Antibodies, Monoclonal
Cells, Cultured
Humans
Immunohistochemistry
Intracellular Membranes ultrastructure
Iodine Radioisotopes
Lysosomes metabolism
Lysosomes ultrastructure
Microscopy, Immunoelectron
Mitochondria ultrastructure
Receptors, Tumor Necrosis Factor analysis
Receptors, Tumor Necrosis Factor immunology
Receptors, Tumor Necrosis Factor, Type I
Tumor Necrosis Factor Decoy Receptors
U937 Cells
Adipocytes metabolism
Carrier Proteins metabolism
Intracellular Membranes metabolism
Mitochondria metabolism
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0023-6837
- Volume :
- 78
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Laboratory investigation; a journal of technical methods and pathology
- Publication Type :
- Academic Journal
- Accession number :
- 9881958