Minimal effects of spargel (PGC-1α) overexpression in a Drosophila mitochondrial disease model

Abstract

PGC-1 and its homologues have been proposed to act as master regulators of mitochondrial biogenesis in animals. Most relevant studies have been conducted in mammals, where interpretation is complicated by the fact that there are three partially redundant members of the gene family. In Drosophila, only a single PGC-1 homologue, spargel (srl), is present in the genome. Here we analyzed the effects of srl overexpression on phenotype and on gene expression in tko25t, a recessive bang-sensitive mutant with a global defect in oxidative phosphorylation, resulting in a deficiency of mitochondrial protein synthesis. In contrast to previous reports, we found only minimal effects of substantial overexpression of srl throughout development, on the expression of a representative set of both mtDNA- and nuclear-encoded OXPHOS- related transcripts, both in tko25t mutant flies and heterozygous controls. Sex and genetic background appeared to influence the expression of the tested genes, but srl overexpression or tko25t itself did not have clear-cut or systematic effects thereon. These studies provide no support to the concept of spargel as a global regulator of mitochondrial biogenesis. Summary blurboverexpression of spargel, the fly PGC-1 homologue proposed as a mitochondrial biogenesis regulator, has minimal effects on the phenotype of tko25t, considered a fly model for mitochondrial disease