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mt-Nd1  -  NADH dehydrogenase 1, mitochondrial

Mus musculus

Synonyms: 0610040O15Rik, Mtnd1, NADH dehydrogenase subunit 1, NADH-ubiquinone oxidoreductase chain 1, ND1, ...
 
 
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Disease relevance of mt-Nd1

 

High impact information on mt-Nd1

  • Incubation of non-Mtf alpha target cells with synthetic peptide ND1 alpha 1-17 (the first 17 amino acid of the ND1 protein of Mtf alpha mice) rendered them susceptible to lysis by MTF alpha-specific cytotoxic T cells (CTLs) [2].
  • We found only one site where all four genomes differed, affecting amino acid residue 6 of ND1, a subunit of NADH dehydrogenase [2].
  • Having defined H2-M3 as the positively selecting MHC molecule, the severely limited number of H2-M3 binding peptides allowed us to characterize an NADH dehydrogenase subunit 1 (ND1)-derived peptide as the physiological ligand of positive selection [3].
  • The N-formyl group at the NH2 terminus of ND1 was essential for Mta activity [4].
  • Competition experiments using N-substituted ND1-alpha peptides showed that an N-formyl peptide receptor on the target cell, which differs from the chemotactic peptide receptor, was required for Mta expression [4].
 

Biological context of mt-Nd1

  • Furthermore, Nd1-/- mice were sensitive to doxorubicin-induced cardiotoxicity with increased numbers of cardiomyocytes apoptosis [5].
  • We characterized the genomic organization of the Nd1 gene, and found that Nd1-L and Nd1-S consist of 16 and nine exons respectively, and that exons I-VIII are shared between them [6].
 

Anatomical context of mt-Nd1

 

Associations of mt-Nd1 with chemical compounds

  • The maternally transmitted Ag is a cell surface product of three gene products: 1) H-2M3a (formerly Hmta), a class I MHC heavy chain; 2) beta 2-microglobulin; and 3) maternally transmitted factor (Mtf), the N-terminus of the mitochondrially encoded ND1 subunit of the reduced form of nicotinamide-adenine dinucleotide dehydrogenase [9].
  • Protective role of Nd1 in doxorubicin-induced cardiotoxicity [5].
  • CONCLUSIONS: Although Nd1 is dispensable for normal mice development, Nd1 plays a protective role in doxorubicin-induced cardiotoxic responses [5].
  • Furthermore, the doxorubicin-induced reduction of Nd1 mRNA expression in NIH3T3 cells was inhibited by treatment of these cells with cycloheximide [8].
 

Other interactions of mt-Nd1

  • We have recently established a TCR transgenic mouse model (C10.4 TCRtrans+) in which the transgenic TCR was selected on the nonclassical MHC class Ib molecule H2-M3 in conjunction with a physiologically occurring peptide derived from the mitochondrial NADH-dehydrogenase subunit 1 gene (9-mer peptide) [10].
 

Analytical, diagnostic and therapeutic context of mt-Nd1

References

  1. Overexpression of Nd1, a novel Kelch family protein, in the heart of transgenic mice protects against doxorubicin-induced cardiomyopathy. Matsudo, Y., Takamori, Y., Fujimura, L., Nishio, S., Sasagawa, K., Komuro, I., Tokuhisa, T., Hatano, M. Transgenic Res. (2006) [Pubmed]
  2. Maternally transmitted histocompatibility antigen of mice: a hydrophobic peptide of a mitochondrially encoded protein. Loveland, B., Wang, C.R., Yonekawa, H., Hermel, E., Lindahl, K.F. Cell (1990) [Pubmed]
  3. Positive selection of an H2-M3 restricted T cell receptor. Berg, R.E., Princiotta, M.F., Irion, S., Moticka, J.A., Dahl, K.R., Staerz, U.D. Immunity (1999) [Pubmed]
  4. Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta. Shawar, S.M., Cook, R.G., Rodgers, J.R., Rich, R.R. J. Exp. Med. (1990) [Pubmed]
  5. Protective role of Nd1 in doxorubicin-induced cardiotoxicity. Fujimura, L., Matsudo, Y., Kang, M., Takamori, Y., Tokuhisa, T., Hatano, M. Cardiovasc. Res. (2004) [Pubmed]
  6. Nd1, a novel murine Kelch family protein, may play the role of a housekeeping gene. Kang, M., Matsudo, Y., Sasagawa, K., Tokuhisa, T., Hatano, M. Biochim. Biophys. Acta (2001) [Pubmed]
  7. Identification of Nd1, a novel murine kelch family protein, involved in stabilization of actin filaments. Sasagawa, K., Matsudo, Y., Kang, M., Fujimura, L., Iitsuka, Y., Okada, S., Ochiai, T., Tokuhisa, T., Hatano, M. J. Biol. Chem. (2002) [Pubmed]
  8. Expression of the Nd1 gene is down-regulated by doxorubicin at post-transcriptional level. Takamori, Y., Matsudo, Y., Fujimura, L., Kang, M., Harada, Y., Moriya, H., Tokuhisa, T., Hatano, M. Int. J. Mol. Med. (2006) [Pubmed]
  9. Biochemical specificity of H-2M3a. Stereospecificity and space-filling requirements at position 1 maintain N-formyl peptide binding. Vyas, J.M., Shawar, S.M., Rodgers, J.R., Cook, R.G., Rich, R.R. J. Immunol. (1992) [Pubmed]
  10. A physiological ligand of positive selection is seen with high specificity. Irion, S., Berg, R.E., Staerz, U.D. J. Immunol. (2000) [Pubmed]
 
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