title: Truncated product of the bifunctional DLST gene involved in biogenesis of the respiratory chain.
abstract: Dihydrolipoamide succinyltransferase (DLST) is a subunit enzyme of the alpha-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.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanamori
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nishimaki
authors.forename: Sadamitsu
authors.initials: S
authors.lastname: Asoh
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Ishibashi
authors.forename: Iichiro
authors.initials: I
authors.lastname: Takata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuwabara
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Shiro
authors.initials: S
authors.lastname: Sugihara
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ihara
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakano
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Matuda
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
mesh_terms: D000217:Acyltransferases / Q000235:genetics* / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D004579:Electron Transport / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000502:physiology; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D018384:Oxidative Stress; D016716:PC12 Cells; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D021122:Protein Subunits; D016337:RNA, Catalytic; D012333:RNA, Messenger; D000217:Acyltransferases; C021515:dihydrolipoamide succinyltransferase