2017 Fiscal Year Final Research Report
Accumulation mechanism of mutant mitochondrial DNA in C. elegans
| Project/Area Number |
15K19029
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Jichi Medical University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Keywords | ミトコンドリアDNA / 欠失型mtDNAの蓄積 / 線虫 / TFAM |
|---|
| Outline of Final Research Achievements |
Accumulation of mitochondrial DNA (mtDNA) containing mutation or deletion will be a cause of mitochondrial disease, however, the molecular mechanism and regulating factors in organisms are largely unknown. In this study, we used C. elegans strain LB138 that contains wild-type and deleted mtDNA molecules in heteroplasmic as a model, to identify the regulatory factors in the process. We knocked down several genes that are involved in mtDNA maintenance in LB138. As a result, we found that knockdown of HMG-5, a homologue of human TFAM, significantly reduced the rate of content of deleted mtDNA per wild-type. We then reduced the amount of mtDNA copy number in LB138 by using a replication inhibitor, and examined the effect. The reduction of mtDNA copy number did not significantly affect the mutant rate, suggesting that HMG-5 is involved in stable maintenance of deleted mtDNA molecule independently of the mtDNA copy number maintenance.
|
| Free Research Field |
分子生物学
|
