Access Type
Open Access Embargo
Date of Award
January 2025
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Molecular Biology and Genetics
First Advisor
Maik Hüttemann
Abstract
Mitochondria are regulated in order to efficiently couple energy production to energy demand. These processes, such as phosphorylations and acetylations on various electron transport chain (ETC) components, can become dysfunctional in the context of certain pathological conditions, such as ischemia-reperfusion injury. Ischemia-reperfusion injury occurs when blood flow is restored to an ischemic tissue, where blood flow was previously blocked. Under basal conditions, inhibitory phosphorylations on cytochrome c (Cytc) and complex IV (cytochrome c oxidase, COX) control mitochondrial activity and work to maintain an optimal, intermediate mitochondrial membrane potential (ΔΨm). During ischemia, these inhibitory phosphorylations are lost, priming the mitochondria for hyperactivity upon reperfusion, which drives reactive oxygen species (ROS) production and, eventually, apoptosis. On the other hand, acetylations of Cytc are typically not present under basal conditions and instead are found in specific disease processes, such as prostate cancer or after ischemia. Specific wavelengths of infrared light (IRL) are known to either stimulate or inhibit mitochondrial activity. Inhibitory IRL would be useful in the context of ischemia-reperfusion injury, where hyperactive mitochondria cause tissue damage. By inhibiting these hyperactive mitochondria, the production of ROS can be prevented until normal mitochondrial homeostasis is restored. In order for IRL to be useful clinically, it must be known how much light is able to penetrate through the head into deep brain structures, which are most vulnerable to ischemia-reperfusion injury during stroke. First, this thesis covers what is known about the endogenous regulation of mitochondrial activity regarding phosphorylations and acetylations of Cytc. Second, a specific acetylation of Cytc, on lysine 7 (K7), is characterized. Third, the dysregulation of Cytc during stroke and how this can be treated by using specific wavelengths of IRL to inhibit COX is presented. Lastly, the penetration of IRL through the human head is studied in a human cadaver model.
Recommended Citation
Morse, Paul Thomas, "The Endogenous Regulation And Exogenous Manipulation Of Mitochondrial Activity: Cytochrome C And Cytochrome C Oxidase" (2025). Wayne State University Dissertations. 4166.
https://digitalcommons.wayne.edu/oa_dissertations/4166