Mitochondrial single-stranded DNA-binding protein is required for mitochondrial DNA replication and development in Drosophila melanogaster

The discovery that several inherited human diseases are caused by mtDNA dep letion has led to an increased interest in the replication and maintenance of mtDNA. We have isolated a new mutant in the lopo (low power) gene from D rosophila melanogaster affecting the mitochondrial single-stranded DNA-bind ing protein (mtSSB), which is one of the key components in mtDNA replicatio n and maintenance. lopo(1) mutants die late in the third instar before comp letion of metamorphosis because of a failure in cell proliferation. Molecul ar, histochemical, and physiological experiments show a drastic decrease in mtDNA content that is coupled with the loss of respiration in these mutant s. However, the number and morphology of mitochondria are not greatly affec ted. Immunocytochemical analysis shows that mtSSB is expressed in all tissu es but is highly enriched in proliferating tissues and in the developing oo cyte. lopo(1) is the first mtSSB mutant in higher eukaryotes, and its analy sis demonstrates the essential function of this gene in development, provid ing an excellent model to study mitochondrial biogenesis in animals.