Title | Functional characterization of drim2, the Drosophila melanogaster homolog of the yeast mitochondrial deoxynucleotide transporter. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Da-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 |
Journal | J Biol Chem |
Volume | 289 |
Issue | 11 |
Pagination | 7448-59 |
Date Published | 2014 Mar 14 |
ISSN | 1083-351X |
Keywords | Amino 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. |
DOI | 10.1074/jbc.M113.543926 |
Alternate Journal | J. Biol. Chem. |
Citation Key | 10.1074/jbc.M113.543926 |
PubMed ID | 24469456 |
PubMed Central ID | PMC3953259 |
Grant List | GGP09019 / / Telethon / Italy GGP11011 / / Telethon / Italy GPP10005 / / Telethon / Italy MC_UP_1002/1 / / Medical Research Council / United Kingdom |