Slirp2 modulates oogenesis via regulating mitochondrial protein translation.

Abstract

Mitochondria are essential organelles responsible for generating adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS). Despite having their own genome, mitochondria rely on a complex interplay with nuclear-encoded proteins to maintain their function, as mutations in these proteins can lead to mitochondrial dysfunction and associated diseases. Mutations in the SLIRP gene are known to cause severe human mitochondrial diseases, and loss of stem-loop interacting RNA-binding protein (SLIRP) function can impair mitochondrial mRNA stability and translation. However, in vivo roles of the SLIRP protein remain inadequately understood. Drosophila melanogaster serves as a powerful model for studying mitochondrial function, particularly in the context of reproductive system development and gametogenesis. In this study, we focus on the role of the fly Slirp2 in oogenesis. Loss of Slirp2 impairs mitochondrial protein synthesis, leading to reduced OXPHOS efficiency, diminished ATP production, and disrupted insulin/mTOR signaling. These defects ultimately promote reactive oxygen species-induced programmed cell death, resulting in infertility. Our findings provide novel insights into the mechanistic role of Slirp2 in mitochondrial function and reproductive biology in vivo. We demonstrate that Slirp2 exhibits species-specific regulation of mitochondrial translation, revealing its complex, context-dependent function. These results have broader implications for understanding mitochondrial diseases, suggesting that the effects of Slirp2 mutations may vary across different organisms and tissue types.