Essential Role of Nucleoside Diphosphate Kinase NME3 on Mitochondrial Morphogenesis
| Autor: | Yu-Chen Chang, 張瑜真 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 The fission and fusion dynamics of mitochondria are crucial for their role in physiological processes and are precisely regulated. As protein machineries governing mitochondrial dynamics have been fully discovered, how lipids affect mitohcondrial morphology remains comparatively unclear. Highly conserved nucleoside diphosphate kinases are previously discovered as GTP fueling enzymes for dynamin superfamily proteins during membrane remodeling processes. Here we demonstrated that NME3 is required for mitochondrial morphology maintenance that depletion of NME3 caused mitochondrial fragmentation in C2C12 myoblast as well as in myotube. Surprisingly, a kinase-dead NME3 could still rescued this phenotype, yet the N-terminus truncated NME3 could not. Utilizing biochemical reconstitution experiments, we found NME3 directly binds to phosphatidic acid (PA) and functions as a mitochondrial tethering protein through the amphipathic helix formation and oligomeric architecture. Together my study proposes a function of amphipathic helix in organelle integrity maintenance and provides a mechanistic explanation for the role of PA in mitofusin-mediated mitochondrial fusion. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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