The Drosophila gene encoding JIG protein (CG14850) is required to modulate nuclear-mitochondrial communication during development

Coordination of mitochondrial and nuclear processes is key to cellular health; however, very little is known about the molecular mechanisms regulating these processes. Here, we report a novel molecular mechanism controlling the shuttling of CREB (cAMP response element-binding protein) protein complex between mitochondria and nucleoplasm. We show that a previously unknown protein, herein termed as Jig, functions as a tissue-specific and developmental timing-specific coregulator in the CREB pathway. Jig is a small protein that shuttles between mitochondria and nucleoplasm. Our results demonstrate that Jig interacts with CrebA protein and controls its delivery to the nucleus, thus triggering CREB-dependent transcription in nuclear chromatin and mitochondria. Ablating the expression of Jig prevents CrebA from localizing to the nucleoplasm, affecting mitochondrial functioning and morphology and leads to Drosophila developmental arrest at the early third instar larval stage. Together, these results implicate Jig as an essential mediator of nuclear and mitochondrial processes. We also found that Jig belongs to a family of nine similar proteins, each of which has its own tissue- and time-specific expression profile. Thus, our results are the first to describe the molecular mechanism regulating nuclear and mitochondrial processes in a tissue- and time-specific manner. Overall design: In total 6 samples: 3 biological replicates of early (1st 12 hrs) 3rd instar larvae from flies expressing JIG-GFP and 3 biological replicates of early 3rd instar larvae from wild type flies.