Decreased mitochondrial function is closely linked to aging and many age-related diseases, including those involving neurodegeneration. These important organelles make ATP, intermediate metabolites, and regulate programmed cell death. To fulfill these roles, mitochondria require proteins and products supplied by the cytoplasm and nucleus, a process that relies on tightly regulated signaling and coordination between the compartments. There are many aspects of the complex relationship between mitochondria and the cytoplasm that we do not fully understand. To better assess the influence of mitochondrial decline on aging and age-related diseases, it is critical to identify and understand the genes and mechanisms controlling mitochondrial function in vivo in multicellular organisms. This is a pressing need due to the causative effect mitochondrial dysfunction has on aging and a variety of age-related diseases. Better knowledge of the underlying mechanisms controlling mitochondrial function will allow us to intelligently design therapeutics to treat mitochondrial diseases and age-related problems due to mitochondrial decline. This in turn will improve public health by helping the public and military health systems.

Mitochondria are cellular organelles that produce the majority of ATP in eukaryotic cells. Mitochondria are unique in that they contain their own DNA, mtDNA. While this DNA is small, approximately 16kb in metazoans, it is critical for normal mitochondrial function. Because mitochondria cannot be made de novo, mitochondria and mtDNA are inherited through the mother’s oocyte cytoplasm. In addition, mtDNA and mitochondria can undergo damage and become non-functional.

In the last twenty years, an increasing number of diseases have been linked to mutations in either mtDNA or nuclear genes encoding mitochondrial proteins. While the general observation that faulty mitochondria can lead to disease may not be surprising given the important role mitochondria play in cellular function, the specificity with which only certain cell types are affected by single mutations has been. In addition, there is mounting evidence for a role of mitochondrial dysfunction in common diseases, such as neurodegenerative disease, diabetes and cardiovascular disease.

  • Current funding support: PRIMER (Precision Medicine Initiative for Medical Education and Research, NHLBI/DoD)
  • Previous funding support: CNRM (Center for Neuroscience and Regenerative Medicine), USU Start Up funds, USU Exploratory grant, NIH/NIGMS, NIH/NINDS


In the Cox lab, we have developed Drosophila as a powerful model system to study mitochondria, combining imaging, genetics and biochemistry. Our long-term goal is to understand the cellular processes responsible for supporting and maintaining functional mitochondria during tissue homeostasis and development.

Broadly, we study how mitochondria change shape, location, physiology, and mtDNA content in response to developmental changes, and we elucidate which genes and molecular pathways regulate these changes. To address these general questions, we use the model system Drosophila melanogaster, or fruit fly. The advantages to using Drosophila are that their rich genetic history allows rapid and straightforward mutant acquisition, and researchers understand much about organ and tissue development. Mitochondria can be imaged in fixed and live tissue at single organelle resolution. It is important to note that an estimated 75% of human disease genes have a functional homolog in flies. The overwhelming similarity of genes and molecular pathways between humans and flies allows us to apply knowledge gained from Drosophila to elucidate the causes of human disease.


The role of Clueless in mitochondrial maintenance

Clueless (Clu) is involved in mitochondrial localization and function. Clu is a highly conserved ribonucleic acid binding protein (RBP) that is required to support mitochondrial function. Drosophila lacking Clu die quickly with damaged, non-functional mitochondria. We have shown Clu binds mRNA and associates with the ribosome. In addition, Clu physically and genetically interacts with components of the mitophagy machinery, PINK1 and Parkin. PINK1 and Parkin are mutated in humans suffering from early-onset Parkinson’s disease. Our current model is that Clu is involved in mitochondrial protein import and may act as a sensor linking protein import to mitochondrial quality control via the mitophagy pathway.

Disease Models & Mechanisms Publication

Biology Open Publication

bioRXiv Publication

Mitochondrial RNase P and disease

Mitochondrial tRNA (mt-tRNAs) are processed on their 5’-end by a three-protein complex called mitochondrial RNase P (mtRNase P). This processing not only matures mt-tRNAs but is also critical for maturation of the other mtRNA species encoded in mtDNA. Human mutations in either the protein complex or mtDNA can decrease processing, leading to mitochondrial dysfunction and disease. We are characterizing the in vivo role of mtRNase P on tissue development and homeostasis to better understand the disease etiology in humans.

Nucleic Acids Research Publication

RNA Metabolism in Mitochondria Textbook