"Tissue" transglutaminase contributes to the formation of disulphide bridges in proteins of mitochondrial respiratory complexes

Pier Giorgio Mastroberardino, Maria Grazia Farrace, Irene Viti, Flaminia Pavone, Gian Maria Fimia, Gennaro Melino, Carlo Rodolfo, Mauro Piacentini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1357-1365
Number of pages9
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1757
Issue number9-10
DOIs
Publication statusPublished - Sep 2006

Keywords

  • ATP synthase
  • HSP60
  • Prohibitin
  • Protein Disulphide Isomerase
  • Respiratory chain complex
  • Transglutaminase 2 knock out mice

ASJC Scopus subject areas

  • Biophysics

Fingerprint Dive into the research topics of '"Tissue" transglutaminase contributes to the formation of disulphide bridges in proteins of mitochondrial respiratory complexes'. Together they form a unique fingerprint.

Cite this