Functional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter.

TitleFunctional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter.
Publication TypeJournal Article
Year of Publication2014
AuthorsDa-Rè, C, Franzolin, E, Biscontin, A, Piazzesi, A, Pacchioni, B, Gagliani, MCristina, Mazzotta, G, Tacchetti, C, Zordan, MA, Zeviani, M, Bernardi, P, Bianchi, V, De Pittà, C, Costa, R
JournalJ Biol Chem
Volume289
Issue11
Pagination7448-59
Date Published2014 Mar 14
ISSN1083-351X
KeywordsAmino Acid Sequence, Animals, Animals, Genetically Modified, Biological Transport, DNA, Mitochondrial, Drosophila melanogaster, Drosophila Proteins, Gene Expression Profiling, Mitochondria, Molecular Sequence Data, Nucleotide Transport Proteins, Nucleotides, Oligonucleotide Array Sequence Analysis, Oxygen Consumption, RNA Interference, RNA, Double-Stranded, Saccharomyces cerevisiae Proteins, Sequence Homology, Amino Acid
Abstract

The CG18317 gene (drim2) is the Drosophila melanogaster homolog of the Saccharomyces cerevisiae Rim2 gene, which encodes a pyrimidine (deoxy)nucleotide carrier. Here, we tested if the drim2 gene also encodes for a deoxynucleotide transporter in the fruit fly. The protein was localized to mitochondria. Drosophila S2R(+) cells, silenced for drim2 expression, contained markedly reduced pools of both purine and pyrimidine dNTPs in mitochondria, whereas cytosolic pools were unaffected. In vivo drim2 homozygous knock-out was lethal at the larval stage, preceded by the following: (i) impaired locomotor behavior; (ii) decreased rates of oxygen consumption, and (iii) depletion of mtDNA. We conclude that the Drosophila mitochondrial carrier dRIM2 transports all DNA precursors and is essential to maintain mitochondrial function.

DOI10.1074/jbc.M113.543926
Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M113.543926
PubMed ID24469456
PubMed Central IDPMC3953259
Grant ListGGP09019 / / Telethon / Italy
GGP11011 / / Telethon / Italy
GPP10005 / / Telethon / Italy
MC_UP_1002/1 / / Medical Research Council / United Kingdom