Novel pharmacological modulators of mitochondrial function in cell physiology and pathology
Abstract/Contents
- Abstract
- Within a single cell, thousands of mitochondria form a beautiful dynamic network. Beyond their canonical adenosine triphosphate (ATP) generating role, mitochondria more recently gained recognition as the hub of numerous signaling pathways that mediate cell life and death. Mitochondria are ubiquitous organelles that play a pivotal role in many organs. It is not therefore not surprising that dysfunctional mitochondria, and the excessive reactive oxygen species (ROS) they produce, have been implicated as the culprits of a variety of disorders spanning multiple body systems. This dissertation describes the development of novel pharmacological tools that target mitochondrial function in cell physiology and pathology. Chapters 1 and 2 introduce mitochondria as attractive therapeutic targets for cardiovascular and neurodegenerative diseases, respectively. Each chapter includes a review of relevant clinical trials and outcomes of therapeutics that either generally target ROS versus ones that specifically target mitochondrial dysfunction. In addition, they highlight the advantages and the challenges of therapeutic avenues involving mitochondria. Chapter 3 summarizes the use of peptides as specific protein-protein interaction (PPI) inhibitors for ameliorating the ischemia-reperfusion (IR) damage associated with myocardial infarction. These novel pharmacological tools target protein kinase C delta ( PKC), which translocates to the mitochondria in response to stress induced by IR and phosphorylates numerous mitochondrial substrates. These PPI peptide inhibitors each specifically inhibit the phosphorylation of one protein substrate. Chapters 4 and 5 focus on the characterization of activators and inhibitors of mitochondrial fission and fusion, the core processes of mitochondrial dynamics. Mitochondrial dynamics govern mitochondrial shape and size, which are tightly linked to function. Dysregulation of these processes is a hallmark of neurodegeneration, in particular Huntington's disease and Charcot Marie Tooth Type IIa, both of which serve as the backdrop model for these newly-identified peptide modulators.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Kornfeld, Opher Shai | |
|---|---|---|
| Degree supervisor | Mochly-Rosen, Daria | |
| Thesis advisor | Mochly-Rosen, Daria | |
| Thesis advisor | Bernstein, Daniel, 1953- | |
| Thesis advisor | Jarosz, Daniel | |
| Thesis advisor | Meyer, Tobias | |
| Degree committee member | Bernstein, Daniel, 1953- | |
| Degree committee member | Jarosz, Daniel | |
| Degree committee member | Meyer, Tobias | |
| Associated with | Stanford University, Department of Chemical and Systems Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Opher Shai Kornfeld. |
|---|---|
| Note | Submitted to the Department of Chemical and Systems Biology. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Opher Shai Kornfeld
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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