Nuclear genomic control of naturally occurring variation in mitochondrial function in Drosophila melanogaster

作者：Jumbo Lucioni Patricia; Bu Su; Harbison Susan T; Slaughter Juanita C; Mackay Trudy F C; Moellering Douglas R^*; De Luca Maria

来源：BMC Genomics, 2012, 13: 659.

DOI：10.1186/1471-2164-13-659

Background: Mitochondria are organelles found in nearly all eukaryotic cells that play a crucial role in cellular survival and function. Mitochondrial function is under the control of nuclear and mitochondrial genomes. While the latter has been the focus of most genetic research, we remain largely ignorant about the nuclear-encoded genomic control of inter-individual variability in mitochondrial function. Here, we used Drosophila melanogaster as our model organism to address this question. %26lt;br%26gt;Results: We quantified mitochondrial state 3 and state 4 respiration rates and P:O ratio in mitochondria isolated from the thoraces of 40 sequenced inbred lines of the Drosophila Genetic Reference Panel. We found significant within-population genetic variability for all mitochondrial traits. Hence, we performed genome-wide association mapping and identified 141 single nucleotide polymorphisms (SNPs) associated with differences in mitochondrial respiration and efficiency (P %26lt;= 1 x 10(-5)). Gene-centered regression models showed that 2-3 SNPs can explain 31, 13, and 18% of the phenotypic variation in state 3, state 4, and P: O ratio, respectively. Most of the genes tagged by the SNPs are involved in organ development, second messenger-mediated signaling pathways, and cytoskeleton remodeling. One of these genes, sallimus (s/s), encodes a component of the muscle sarcomere. We confirmed the direct effect of s/s on mitochondrial respiration using two viable mutants and their coisogenic wild-type strain. Furthermore, correlation network analysis revealed that s/s functions as a transcriptional hub in a co-regulated module associated with mitochondrial respiration and is connected to CG7834, which is predicted to encode a protein with mitochondrial electron transfer flavoprotein activity. This latter finding was also verified in the s/s mutants. %26lt;br%26gt;Conclusions: Our results provide novel insights into the genetic factors regulating natural variation in mitochondrial function in D. melanogaster. The integrative genomic approach used in our study allowed us to identify s/s as a novel hub gene responsible for the regulation of mitochondrial respiration in muscle sarcomere and to provide evidence that s/s might act via the electron transfer flavoprotein/ubiquinone oxidoreductase complex.

• 出版日期2012-11-22