Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain

AUTOR(ES)

Kanamori, Takashi

FONTE

Oxford University Press

RESUMO

Dihydrolipoamide succinyltransferase (DLST) is a subunit enzyme of the α-ketoglutarate dehydrogenase complex of the Krebs cycle. While studying how the DLST genotype contributes to the pathogenesis of Alzheimer’s disease (AD), we found a novel mRNA that is transcribed starting from intron 7 in the DLST gene. The novel mRNA level in the brain of AD patients was significantly lower than that of controls. The truncated gene product (designated MIRTD) localized to the intermembrane space of mitochondria. To investigate the function of MIRTD, we established human neuroblastoma SH-SY5Y cells expressing a maxizyme, a kind of ribozyme, that specifically digests the MIRTD mRNA. The expression of the maxizyme specifically eliminated the MIRTD protein and the resultant MIRTD-deficient cells exhibited a marked decrease in the amounts of subunits of complexes I and IV of the mitochondrial respiratory chain, resulting in a decline of activity. A pulse-label experiment revealed that the loss of the subunits is a post-translational event. Thus, the DLST gene is bifunctional and MIRTD transcribed from the gene contributes to the biogenesis of the mitochondrial respiratory complexes.

Documentos Relacionados

• The narJ gene product is required for biogenesis of respiratory nitrate reductase in Escherichia coli.
• A conserved function of YidC in the biogenesis of respiratory chain complexes
• A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts
• Identification of the SAAT Gene Involved in Strawberry Flavor Biogenesis by Use of DNA Microarrays
• Biogenesis of respiratory cytochromes in bacteria.