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The genetic basis of mitochondrial DNA depletion syndrome (958.2)
Author(s) -
Venkataraman Chantel,
Field Martha,
Stover Patrick
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.958.2
Subject(s) - mitochondrial dna , biology , nucleotide , hela , microbiology and biotechnology , gene , mitochondrion , uracil , genetics , dna , cell culture
Mutations in DGUOK, a gene encoding an enzyme in the mitochondrial nucleotide synthesis salvage pathway, and MPV17, a gene encoding an inner mitochondrial membrane protein of unknown function, have been shown to cause the hepatocerebral form of mitochondrial DNA depletion syndrome. MPV17 has been postulated to function as a nucleotide transporter. Transient HeLa cell culture models using siRNA and stable HeLa cell culture models using shRNA were created. The models facilitated studies addressing the effects of nucleotide availability on mtDNA copy number. It was observed that mtDNA copy number modestly decreased in MPV17 siRNA cells cultured in nucleotide replete medium. Supplementation with nucleotides individually indicates that pyrimidine availability increases mtDNA copy number in MPV17 siRNA‐treated cells as much as 10‐fold. Further experiments to determine the quality of the mtDNA through determination of uracil content are currently being conducted. Grant Funding Source : Supported by NIH R37DK58144