1993 Fiscal Year Final Research Report Summary
Molecular Pathology on Mitochondrial Encepholomyopathy
| Project/Area Number |
04670151
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Jichi Medical School |
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Principal Investigator |
OHTA Shigeo 自治医科大学, 医学部, 助教授 (00125832)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Mitochondria / Encepholomyopathy / Mitochondrial DNA / tRNA / Genetic Disease / Protein Synthesis |
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| Research Abstract |
A new mitochondrial DNA (mtDNA) mutation of tRNA^<Leu(UUR)> at nucleotide position 3271 (MELAS3271) was determined to be involved in the pathogenic process of mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) using intercellular transfer of patient-derived mtDNA to mtDNA-less HeLa cells (p^0 HeLa cells). Cybrid clones containing imported mtDNA exclusively from a MELAS patient with MELAS3271 mtDNA were isolated, and the influence of MELAS3271 mtDNA on mitochondrial translation activity and mitochondrial respiratory complex I enzyme activity were examined. Accumulation of more than 87% MELAS3271 mutant mtDNA in the cybrid clones induced both low complex I activity and abnormal mtDNA-encoded polypeptide synthesis including at least complex I subunit ND6, suggesting involvement of the new MELAS-associated mutation in the pathogenesis.
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