Mutations of the <i>Gongpo</i> Gene Encoding a Homolog of Mammalian Phosphatidylserine Synthases Cause Neurodegeneration in <i>Drosophila Melanogaster</i>

Abstract

Phosphatidylserine (PS) is an integral phospholipid component of eukaryotic cell membranes and organelles. The Drosophila genome contains a single PS synthase-encoding gene (Gongpo, Gong for short) with a protein sequence homologous to mammalian PS synthases. In this study, we characterize mutant Gong phenotypes. Adult flies with trans-heterozygous and heterozygous mutations for Gong loss-of-function alleles had reduced life span, increased bang sensitivity, locomotor defects, and increased formation of vacuoles in the brain, a sign associated with neurodegenerative disorders. Similar phenotypes were observed with pan-glial-specific knockdown/overexpression of Gong, but not with pan-neuronal manipulations. We observed defective mitochondria in the mutant adult brain, elevated production of reactive oxygen species, and increased autophagy and apoptotic cell death. These findings suggest that proper expression of Gong in glia is essential for the development and maintenance of brain function. We propose a new mechanism for neurodegenerative disease, triggered by defective PS metabolism in the nervous system.