TY - JOUR
T1 - "Tissue" transglutaminase contributes to the formation of disulphide bridges in proteins of mitochondrial respiratory complexes
AU - Mastroberardino, Pier Giorgio
AU - Farrace, Maria Grazia
AU - Viti, Irene
AU - Pavone, Flaminia
AU - Fimia, Gian Maria
AU - Melino, Gennaro
AU - Rodolfo, Carlo
AU - Piacentini, Mauro
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
KW - ATP synthase
KW - HSP60
KW - Prohibitin
KW - Protein Disulphide Isomerase
KW - Respiratory chain complex
KW - Transglutaminase 2 knock out mice
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U2 - 10.1016/j.bbabio.2006.07.007
DO - 10.1016/j.bbabio.2006.07.007
M3 - Article
C2 - 16979579
AN - SCOPUS:33748957546
VL - 1757
SP - 1357
EP - 1365
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 0005-2728
IS - 9-10
ER -