Date of Award
Spring 5-15-2018
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Despite considerable effort to develop neuro and cardioprotective drugs there remains no treatment other than restoration of blood flow to treat hypoxic/ischemic injuries such as strokes and myocardial infarctions. This implies that our understanding of the basic mechanisms behind hypoxic injury is lacking. Recent studies have identified protein homeostatic (proteostatic) disruptions as playing a role in hypoxic injury. Yet, most of these studies have focused on cytoplasmic or endoplasmic reticulum (ER) proteostasis, with little attention to possible contributions of mitochondrial proteostasis. In order to address this gap in our knowledge I have performed experiments to determine if mitochondrial proteostasis is disrupted by hypoxia and if activators of mitochondrial proteostatic mechanisms such as the mitochondrial unfolded protein response (mtUPR) can protect against hypoxic injury. In order to begin to identify the mechanisms of proteostatic disruption following hypoxia I have identified mitochondrial proteins prone to aggregation following hypoxia and identified a number of other physiologic stressors that lead to mitochondrial proteostatic disruptions. Additionally I have conducted a small molecule screen to identify novel activators of the mtUPR.
Language
English (en)
Chair and Committee
C. Michael Crowder
Committee Members
Aaron DiAntonio, Abhinav Diwan, S. Kerry Kornfeld, Michael Nonet,
Recommended Citation
Kaufman, Daniel Martin, "Mitochondrial Proteostasis and Hypoxic Injury" (2018). Arts & Sciences Electronic Theses and Dissertations. 1546.
https://openscholarship.wustl.edu/art_sci_etds/1546
Included in
Cell Biology Commons, Family, Life Course, and Society Commons, Gerontology Commons, Neuroscience and Neurobiology Commons
Comments
Permanent URL: https://doi.org/10.7936/K7QZ29FQ