Genetic and functional analysis of mitochondrial DNA-encoded complex I genes

Yidong Bai, Peiqing Hu, Jeong Soon Park, Jian Hong Deng, Xiufeng Song, Anne Chomyn, Takao Yagi, Giuseppe Attardi

Producción científica: Articlerevisión exhaustiva

37 Citas (Scopus)


Mammalian mitochondrial NADH dehydrogenase (complex I) is a multimeric complex consisting of at least 45 subunits, 7 of which are encoded by mitochondrial DNA (mtDNA). The function of these subunits is largely unknown. We have established an efficient method to isolate and characterize cells carrying mutations in various mtDNA-encoded complex I genes. With this method, 15 mouse cell lines with deficiencies in complex I-dependent respiration were obtained, and two near-homoplasmic mutations in mouse ND5 and ND6 genes were isolated. Furthermore, by generating a series of cell lines with the same nuclear background but different content of an mtDNA nonsense mutation, we analyzed the genetic and functional thresholds in mouse mitochondria. We found that in wild-type cells, about 40% of ND5 mRNA is in excess of that required to support a normal rate of ND5 subunit synthesis. However, there is no indication of compensatory upsurge in either transcription or translation with the increase in the proportion of mutant ND5 genes. Interestingly, the highest ND5 protein synthesis rate was just sufficient to support the maximum complex I-dependent respiration rate, suggesting a tight regulation at the translational level. In another line of research, we showed that the mitochondrial NADH-quinone oxidoreductase of Saccharomyces cerevisiae (NDI1), although consisting of a single subunit, can completely restore respiratory NADH dehydrogenase activity in mutant human cells that lack the essential mtDNA-encoded subunit ND4. In particular, in these transfected cells, the yeast enzyme becomes integrated into the human respiratory chain and fully restores the capacity of the cells to grow in galactose medium.

Idioma originalEnglish (US)
Páginas (desde-hasta)272-283
Número de páginas12
PublicaciónAnnals of the New York Academy of Sciences
EstadoPublished - 2004

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Neuroscience
  • History and Philosophy of Science


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