상세정보
Export to Refworks부가기능
The Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles
상세 프로파일
| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Regulation of Mitochondrial Complex I Biogenesis in Drosophila Flight Muscles. |
| 개인저자 | Garcia, Christian Joel. |
| 단체저자명 | Columbia University. Nutritional and Metabolic Biology. |
| 발행사항 | [S.l.]: Columbia University., 2020. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2020. |
| 형태사항 | 242 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781392888735 |
| 학위논문주기 | Thesis (Ph.D.)--Columbia University, 2020. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Owusu-Ansah, Edward. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Mitochondrial Complex I (CI) is composed of 44 distinct subunits that are assembled with eight Fe- S clusters and a single flavin mononucleotide. Mitochondria is highly enriched in the flight muscles of Drosophila melanogaster, however the assembly mechanism of Drosophila CI has not been described. We report that the mechanism of CI biogenesis in Drosophila flight muscles proceeds via the formation of ~315- , ~550-, and ~815 kDa CI assembly intermediates. Additionally, we define specific roles for several CI subunits in the assembly process. In particular, we show that dNDUFS5 is required for converting the ~700 kDa transient CI assembly intermediate into the ~815 kDa assembly intermediate, by stabilizing or promoting the incorporation of dNDUFA10 into the complex. Our findings highlight the potential values of Drosophila as a suitable model organism and resource to study the CI biogenesis in vivo, and to address questions relevant to CI biogenesis in humans.CI biogenesis is regulated by transient interactors known as CI assembly factors (CIAFs). To date, about half of CI disorders are attributed to the mutations in the CI subunits and the known CIAFs. The cause for the other half remains to be discovered, warranting the investigation for additional regulators of CI biogenesis such as novel CIAFs. To identify novel regulators, we cataloged interactors of a core subunit, NDUFS3, knocked each one down by RNAi in the Drosophila flight muscle, and analyzed its effect in the stability of CI by blue-native PAGE. We identified the Drosophila Fragile X Mental Retardation protein (dFMRP) to destabilize the holoenzyme of CI and cause it to misassemble. Therefore, we report dFMRP as a novel regulator of CI biogenesis, and demonstrate the utilization of Drosophila as an effective model system to uncover the mysteries of CI biogenesis. |
| 일반주제명 | Physiology. Biochemistry. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
