"Tissue" transglutaminase contributes to the formation of disulphide bridges in proteins of mitochondrial respiratory complexes.
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.
Mastroberardino
Pier Giorgio
PG
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Farrace
Maria Grazia
MG
Viti
Irene
I
Pavone
Flaminia
F
Fimia
Gian Maria
GM
Melino
Gennaro
G
Rodolfo
Carlo
C
Piacentini
Mauro
M
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*
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