Date Approved

12-2022

Document Type

Dissertation

Degree Name

PhD in Molecular Cell Biology & Neuroscience

Department

Graduate School of Biomedical Sciences

College

School of Osteopathic Medicine

First Advisor

Michael Henry, PhD

Committee Member 1

Natalia Shcherbik, PhD

Committee Member 2

Mikhail Anikin, PhD

Committee Member 3

Eric Moss, PhD

Committee Member 4

Dmitry Temiakov, PhD

Subject(s)

Saccharomyces cerevisiae, Genes, Mitochondrial, Mitochondria, Gene Expression Regulation

Disciplines

Cell Biology | Fungi | Laboratory and Basic Science Research | Medicine and Health Sciences | Molecular Biology | Molecular Genetics

Abstract

Although the cytosolic and bacterial translation systems are well studied, much less is known about translation in mitochondria. In the yeast Saccharomyces cerevisiae, mitochondrial gene expression is predominately regulated by translational activators. These regulators are thought to promote translation by binding the elongated 5’-UTRs on their target mRNAs. Since mammalian mitochondrial mRNAs generally lack 5’-UTRs, they must regulate translation by other mechanisms. As expected, most yeast translational activators lack orthologues in mammals. Recently, a mitochondrial gene-specific translational activator, TACO1, was reported in mice and humans. To better define its role in mitochondrial translation I examined the yeast TACO1 orthologue, DPC29. Unexpectedly, I found this protein to act as a general mitochondrial translation factor, rather than a gene-specific translational activator. I also report that human TACO1 and its yeast orthologue are functionally conserved. This demonstrates that information gained from yeast TACO1 should be applicable to humans.

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