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Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain
Author(s) -
Kanamori Takashi,
Nishimaki Kiyomi,
Asoh Sadamitsu,
Ishibashi Yoshitomo,
Takata Iichiro,
Kuwabara Tomoko,
Taira Kazunari,
Yamaguchi Haruyasu,
Sugihara Shiro,
Yamazaki Tsuneo,
Ihara Yasuo,
Nakano Kyoko,
Matuda Sadayuki,
Ohta Shigeo
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg299
Subject(s) - biology , gene product , respiratory chain , gene , mitochondrion , biogenesis , protein subunit , microbiology and biotechnology , phosphofructokinase 2 , messenger rna , mitochondrial biogenesis , gene expression , biochemistry
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.