title: "Tissue" transglutaminase contributes to the formation of disulphide bridges in proteins of mitochondrial respiratory complexes.
abstract: In this study we provide the first in vivo evidences showing that, under physiological conditions, "tissue" transglutaminase (TG2) might acts as a protein disulphide isomerase (PDI) and through this activity contributes to the correct assembly of the respiratory chain complexes. Mice lacking TG2 exhibit mitochondrial energy production impairment, evidenced by decreased ATP levels after physical challenge. This defect is phenotypically reflected in a dramatic decrease of motor behaviour of the animals. We propose that the molecular mechanism, underlying such a phenotype, resides in a defective disulphide bonds formation in ATP synthase (complex V), NADH-ubiquinone oxidoreductase (complex I), succinate-ubiquinone oxidoreductase (complex II) and cytochrome c oxidase (complex IV). In addition, TG2-PDI might control the respiratory chain by modulating the formation of the prohibitin complexes. These data elucidate a new pathway that directly links the TG2-PDI enzymatic activity with the regulation of mitochondrial respiratory chain function.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Mastroberardino
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Farrace
authors.forename: Irene
authors.initials: I
authors.lastname: Viti
authors.forename: Flaminia
authors.initials: F
authors.lastname: Pavone
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Gennaro
authors.initials: G
authors.lastname: Melino
authors.forename: Carlo
authors.initials: C
authors.lastname: Rodolfo
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003432:Cross-Linking Reagents / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000091402:Prohibitins; D019704:Protein Disulfide-Isomerases / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D021122:Protein Subunits / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013379:Substrate Specificity; D011503:Transglutaminases / Q000172:deficiency / Q000378:metabolism*
chemical_list: D003432:Cross-Linking Reagents; D004220:Disulfides; D024101:Mitochondrial Proteins; D000091402:Prohibitins; D021122:Protein Subunits; D012097:Repressor Proteins; D000255:Adenosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D019704:Protein Disulfide-Isomerases