Mppa sustains cyst stem cell maintenance and orchestrates germ cell differentiation through nonautonomous regulation of mitochondrial homeostasis in Drosophila testes

Abstract

Abstract The intricate balance maintaining CySCs and facilitating their differentiation within the testicular stem cell niche remains a complex process. However, the mechanisms underlying CySC maintenance and their nonautonomous impact on GSC differentiation and downstream effects remain elusive. This study elucidates the pivotal role of Mppa in orchestrating the stem cell niche and germ cell differentiation in Drosophila testes. Through targeted manipulation of Mppa levels in the CySC lineage, we uncovered CySC maintenance and germ cell differentiation defects. We further discovered Mppa as a conserved mitochondrial protein crucial for maintaining ATP homeostasis. Transcriptomic analysis revealed Mppa’s influence on mitochondrial function, particularly through pathways involving cytochrome P450. Furthermore, our exploration of Mppa-binding proteins via LC–MS/MS identified associations with diverse energy metabolism processes, oxidation–reduction reactions, and cellular redox balance, with specific interactions validated, such as UQCR-C1. This comprehensive investigation unveils Mppa’s pivotal function in governing nonautonomous germ cell differentiation through energy equilibrium in Drosophila testes, providing novel insights into spermatogenesis disorders linked to disrupted germ cell differentiation. Clinical trial number Not applicable.