Mitochondrial N-formylmethionyl proteins as chemoattractants for neutrophils.
Mitochondria synthesize several hydrophobic proteins. Like bacteria, mitochondria initiate protein synthesis with an N-formylmethionine residue. Because N-formylmethionyl peptides have been found to be chemotactic for polymorphonuclear leukocytes (PMN), mitochondria isolated from cultured human cells and purified bovine mitochondrial proteins were tested for PMN chemotactic activity in vitro. Nondisrupted mitochondria were not chemotactic. However, intact mitochondria that had been incubated with a lysosomal lysate did stimulate PMN migration. Antibodies directed against two mitochondrial enzymes, cytochrome oxidase and ATPase, (both of which contain mitochondrially synthesized subunits) but not anti-C3 or anti-C5 decreased mitochondrially derived chemotactic activity. In addition, purified bovine mitochondrial N-formylmethionyl proteins stimulated PMN migration in vitro, whereas nonformylated mitochondrial proteins did not. Furthermore, the chemotactic activity of purified mitochondrial proteins and disrupted mitochondria was decreased by the formyl peptide antagonist butyloxycarbonyl-phenylalanine-leucine-phenylalanine-leucine-phenylalanine. Finally, disrupted mitochondria and purified mitochondrial proteins stimulated PMN-directed migration (chemotaxis), according to accepted criteria. In addition to other chemotactic factors, release of N-formylmethionyl proteins from mitochondria at sites of tissue damage, may play a role in the accumulation of inflammatory cells at these sites.
D000251:Adenosine Triphosphatases / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003576:Electron Transport Complex IV / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives*; D008928:Mitochondria / Q000378:metabolism*; D009239:N-Formylmethionine / Q000494:pharmacology*; D009504:Neutrophils; D009842:Oligopeptides / Q000494:pharmacology
D009842:Oligopeptides; D009239:N-Formylmethionine; C033373:butyloxycarbonyl-phenylalanyl-leucyl-phenylalanyl-leucyl-phenylalanine; D008715:Methionine; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases