Investigating the function of a mitochondrial phosphatase, PTPMT1, in Drosophila melanogaster
Abstract/Contents
- Abstract
- Mitochondria are complex organelles that play a variety of critical roles in the cell beyond the generation of ATP. Reversible phosphorylation, mediated by mitochondrially-localized kinases and phosphatases, is a central mechanism by which mitochondrial activities are regulated and by which tissue-specific mitochondrial functions can be achieved. PTPMT1 is a mitochondrial phosphatase and a vital regulator of mitochondrial activities. Current work points to roles for PTPMT1 in the regulation of mitochondrial respiration, dynamics, and ultrastructure through the modulation of pyruvate importation, the tuning of TCA cycle activity, and the synthesis of cardiolipin. PTPMT1 is ubiquitously expressed; however, little is known about its tissue-specific functions. Additionally, PTPMT1 has predominately been studied in vertebrate models, even though invertebrate models, namely Drosophila melanogaster, provide powerful genetic tools for the dissection of gene function. In Chapter 1 of this dissertation, I review the current knowledge surrounding PTPMT1 in vertebrate models. In Chapter 2, I introduce the Drosophila tracheal system and briefly review what is known concerning the mechanisms of tracheal liquid clearance and gas filling in the fly. In Chapter 3, I use RNA interference and CRISPR-Cas9 technologies to generate and validate Drosophila models of dPTPMT1 depletion. Using these models, I discover a new physiological role for dPTPMT1 in the process of tracheal liquid clearance and gas filling. I further show that gas-filling defects occur following molting in first instars with tracheal-specific knockdown of dPTPMT1 and are accompanied by subsequent activation of innate immune responses. First instars with dPTPMT1-depleted tracheae show mitochondrial clustering prior to failure of liquid clearance and gas filling, suggesting that an initial mitochondrial defect may be responsible for this phenotype. I further ask whether other mutants in the cardiolipin synthesis pathway phenocopy the tracheal phenotypes observed in dPTPMT1-depletion and find that they do not, indicating that dPTPMT1 likely acts through one of its other known substrates or perhaps through a novel substrate to mediate tracheal liquid clearance and gas filling in Drosophila. My work demonstrates a new cell-type specific role for dPTPMT1 in fly tracheal epithelial cells and establishes a new model for the exploration of dPTPMT1's physiological and cellular functions
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Papakyrikos, Amanda Marie |
|---|---|
| Degree supervisor | Wang, Xinnan |
| Thesis advisor | Wang, Xinnan |
| Thesis advisor | Fuller, Margaret T, 1951- |
| Thesis advisor | Reimer, Richard J |
| Thesis advisor | Talbot, William S |
| Degree committee member | Fuller, Margaret T, 1951- |
| Degree committee member | Reimer, Richard J |
| Degree committee member | Talbot, William S |
| Associated with | Stanford University, Department of Developmental Biology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Amanda Marie Papakyrikos |
|---|---|
| Note | Submitted to the Department of Developmental Biology |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Amanda Marie Papakyrikos
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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