Date of Award

January 2022

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biomedical Sciences

First Advisor

Alexei V. Tulin

Abstract

Despite Drosophila being one of the most studied model organisms in the world of research, one-third of 14,000 protein-encoding genes that the Drosophila genome possesses code for proteins that are yet uncharacterized. While investigating some of these uncharacterized Drosophila proteins, we identified a scarce protein type–a protein localized in both mitochondria and nucleus. Proteins, dual-localized in mitochondria and nucleus, establish communication between these organelles. This type of dual-localized protein is among the rarest of proteins, which limits us from fully understanding the mito-nuclear communication mechanism. Here, we tell the story of Jig, which we discovered to be one of those extremely rare proteins that localize in mitochondria, bind to the mitochondrial genome, localize in the nucleus, and bind to the nuclear genome. To my knowledge, I am the first to show that this rare protein is part of the CREB pathway, which is one of the most studied proteins for the mito-nuclear communication mechanism. Jig binds to and transports CREB from mitochondria to nucleus throughout the 3rd larval developmental stage. The Jig-CREB pair binds to DNA in both mitochondrial and nuclear genomes to regulate genes that are necessary for Drosophila development. Knocking down Jig causes disruption of CREB localization to the nucleus, changes mitochondrial morphology and membrane potential and arrests Drosophila development. These results are the first to show a Jig-CREB pathway that is necessary to conduct mito-nuclear communication for development.

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