Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction
Thesis: Ph. D. in Health Sciences and Technology: Computer Science, Harvard-MIT Program in Health Sciences and Technology, 2017.
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | eng |
| Published: |
Massachusetts Institute of Technology
2018
|
| Subjects: | |
| Online Access: | http://hdl.handle.net/1721.1/113788 |
| _version_ | 1811073918454202368 |
|---|---|
| author | Jain, Isha Himani |
| author2 | Vamsi K. Mootha. |
| author_facet | Vamsi K. Mootha. Jain, Isha Himani |
| author_sort | Jain, Isha Himani |
| collection | MIT |
| description | Thesis: Ph. D. in Health Sciences and Technology: Computer Science, Harvard-MIT Program in Health Sciences and Technology, 2017. |
| first_indexed | 2024-09-23T09:40:13Z |
| format | Thesis |
| id | mit-1721.1/113788 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T09:40:13Z |
| publishDate | 2018 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1137882019-04-11T06:54:24Z Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction Focus on mitochondrial And peroxisomal dysfunction Jain, Isha Himani Vamsi K. Mootha. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Harvard--MIT Program in Health Sciences and Technology. Thesis: Ph. D. in Health Sciences and Technology: Computer Science, Harvard-MIT Program in Health Sciences and Technology, 2017. Cataloged from PDF version of thesis. Includes bibliographical references. Variations in atmospheric oxygen levels can be traced over evolutionary time and track closely with the development of multicellular life, speciation events, appearance of placental mammals and the creation of a cardio-respiratory system. As the final electron acceptor for aerobic ATP production, oxygen allows energy-intensive metabolic pathways to exist. Furthermore, oxygen is the most utilized substrate for known biochemical reactions, surpassing even ATP and NAD+. As a result, variations in oxygen levels have far-reaching consequences on human physiology and health. Mitochondrial disorders are the most common inborn errors of metabolism, affecting approximately 1 in 5000 live births. Patients can present in infancy or adulthood with symptoms affecting multiple organ systems including blindness, deafness, muscle weakness, developmental delay and severe neurological impairment. Unfortunately, there are currently no proven therapies for mitochondrial disorders. My thesis work has focused on combining systems biology, animal physiology and cellular metabolism approaches to develop new therapies for these disorders. More specifically, I have identified hypoxic breathing, equivalent to living at 4500m altitude, as protective in the setting of severe mitochondrial disease. First, I performed a genetic screen and found paradoxically, that hypoxic breathing and hypoxia responses are protective in mitochondrial disease. I then characterized the physiology and preclinical regimens of hypoxia therapy, laying the groundwork for translation to human patients. Fascinated by such a vital role for oxygen in human disease, I went on to define adaptive pathways in varying oxygen tensions. This work highlights the differential reliance on entire organelles at extreme oxygen levels. And finally, I studied the metabolic and proteomic consequences of defects in peroxisome metabolism and disease. by Isha Himani Jain. Ph. D. in Health Sciences and Technology: Computer Science 2018-02-16T20:05:50Z 2018-02-16T20:05:50Z 2017 2017 Thesis http://hdl.handle.net/1721.1/113788 1022847989 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 151 pages application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard--MIT Program in Health Sciences and Technology. Jain, Isha Himani Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title | Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title_full | Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title_fullStr | Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title_full_unstemmed | Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title_short | Oxygen, the invisible orchestrator of metabolism and disease : a focus on mitochondrial And peroxisomal dysfunction |
| title_sort | oxygen the invisible orchestrator of metabolism and disease a focus on mitochondrial and peroxisomal dysfunction |
| topic | Harvard--MIT Program in Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/113788 |
| work_keys_str_mv | AT jainishahimani oxygentheinvisibleorchestratorofmetabolismanddiseaseafocusonmitochondrialandperoxisomaldysfunction AT jainishahimani focusonmitochondrialandperoxisomaldysfunction |