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

J Biol Chem. 2014 Mar 14;289(11):7448-59. doi: 10.1074/jbc.M113.543926. Epub 2014 Jan 27.

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.

Keywords: Drosophila; Mitochondria; Mitochondrial DNA; Mitochondrial Transport; Nucleotide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Biological Transport
  • DNA, Mitochondrial / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Gene Expression Profiling
  • Mitochondria / metabolism*
  • Molecular Sequence Data
  • Nucleotide Transport Proteins / genetics
  • Nucleotide Transport Proteins / metabolism*
  • Nucleotides / chemistry
  • Oligonucleotide Array Sequence Analysis
  • Oxygen Consumption
  • RNA Interference
  • RNA, Double-Stranded / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Sequence Homology, Amino Acid

Substances

  • DNA, Mitochondrial
  • Drosophila Proteins
  • Nucleotide Transport Proteins
  • Nucleotides
  • RIM2 protein, S cerevisiae
  • RNA, Double-Stranded
  • Rim2 protein, Drosophila
  • Saccharomyces cerevisiae Proteins