Analysis of a Novel Infantile Cardioencephalomyopathy-Associated Mutation in Yeast Genetic Model

Elinor Stanley, University of Nebraska - Lincoln

Document Type Thesis

Copyright Elinor Stanley 2022.

Abstract

Analyses performed by Dr. Khalimonchuk’s lab identified a set of potential functional interactions between heme a and a₃ in Cox1. Cytochrome c oxidase is essential for catalysis and the stability/folding of Cox1, and therefore is essential for heme a function. Heme a is generated through a two-step heme reaction by the evolutionarily conserved axis formed by the terminal heme biosynthetic enzyme ferrochelatase (FECH) and two heme-modifying enzymes, Cox10 and Cox15. Further analysis has determined that lack of the Cox enzyme has severe medical issues, such as human mitochondrial myopathies. With this thesis, we provide insights into the pathogenic mechanism of the novel Cox15 disease mutation, and that mutations in Cox15 have major effects on heme levels and cytochrome c oxidas (CcO) function and therefore effects mitochondria oxidative phosphorylation diseases.