Minimal effects ofspargel(PGC-1) overexpression in aDrosophilamitochondrial disease model

Abstract

PGC-1α 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 tko^25t, a recessive bang-sensitive mutant with a global defect in oxidative phosphorylation, resulting from a deficiency of mitochondrial protein synthesis. In contrast to previous reports, we found that substantial overexpression of srl throughout development had only minimal effects on the tko^25t mutant phenotype. Copy number of mtDNA was unaltered and srl overexpression produced no systematic effects on a representative set of transcripts related to mitochondrial OXPHOS and other metabolic enzymes, although these were influenced by sex and genetic background. This study provides no support to the concept of Spargel as a global regulator of mitochondrial biogenesis, at least in the context of the tko^25t model.