Advisory Committee Chair
Victor M Darley-Usmar
Advisory Committee Members
John C Chatham
Yabing Chen
Louis J Dell'Italia
C Roger White
Document Type
Dissertation
Date of Award
2011
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
The mitochondrion plays a central role in the maintenance of bioenergetic function through the production of ATP and essential metabolites. The development of mitochondrial bioenergetic defects is a hallmark of important pathologies such as cardiovascular and liver diseases. It is well established that a decrease in mitochondrial function, typically of 20-40%, is associated with the progression of these pathologies. Causal relationships have been more difficult to establish because of the challenge of assessing mitochondrial function in a cellular setting. Specifically, it is known that mitochondria function at less than their maximal respiratory capacity and the remainder, known as reserve or spare capacity, is thought to be utilized for increased work or combatting oxidative stress. The following questions have been addressed in this dissertation: 1) Does reserve capacity change under conditions of diminished oxygen availability?, 2) Do the variations in mitochondrial phenotype caused by differences in the mitochondrial DNA sequence amongst different populations modify the response to a pathological stress?, and 3) Does the metabolism of alcohol in the liver interact with the mitochondria to change reserve capacity and the response to nitric oxide and hypoxia? In testing these concepts, we have used in vivo models of alcoholic liver disease and cardiac volume overload and an ex vivo model of vascular ischemia/reperfusion. Taken together, our data support the concept that mitochondrial bioenergetics are a key determinant of the response of a wide variety of cells to pathological stressors.
Recommended Citation
Zelickson, Blake Reid, "Assessment of Mitochondrial Stressors on Cellular Bioenergetics" (2011). All ETDs from UAB. 3433.
https://digitalcommons.library.uab.edu/etd-collection/3433