| RRC ID |
61886
|
| 著者 |
Wan Z, Xu J, Huang Y, Zhai Y, Ma Z, Zhou B, Cao Z.
|
| タイトル |
Elevating bioavailable iron levels in mitochondria suppresses the defective phenotypes caused by PINK1 loss-of-function in Drosophila melanogaster.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, which is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Iron deposit was found in the SNpc of PD patients and animal models, however, the mechanisms involved in disturbed iron metabolism remain unknown. Identifying the relationship between iron metabolism and PD is important for finding new therapeutic strategies. In this study, we found that transgenic overexpression (OE) of Drosophila mitoferrin (dmfrn) or knockdown of Fer3HCH significantly mitigated the reduced mitochondrial aconitase activity, abnormal wing posture, flight deficits and mitochondrial morphology defects associated with PINK1 loss-of-function (LOF). Further work demonstrated that dmfrn OE or Fer3HCH knockdown significantly rescued the impaired mitochondrial respiration in PINK1 LOF flies, indicating that dmfrn or Fer3HCH may rescue PINK1 LOF phenotypes through elevating mitochondrial bioavailable iron levels to promote mitochondrial respiration.
|
| 巻・号 |
532(2)
|
| ページ |
285-291
|
| 公開日 |
2020-11-5
|
| DOI |
10.1016/j.bbrc.2020.08.002
|
| PII |
S0006-291X(20)31547-3
|
| PMID |
32873392
|
| MeSH |
Aconitate Hydratase / metabolism
Animals
Animals, Genetically Modified
Basic Helix-Loop-Helix Transcription Factors / genetics
Biological Availability
Drosophila Proteins / genetics*
Drosophila Proteins / metabolism
Drosophila melanogaster / genetics
Gene Expression
Iron / metabolism*
Loss of Function Mutation
Mitochondria / drug effects
Mitochondria / genetics
Mitochondria / metabolism*
Nerve Tissue Proteins / genetics
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Rotenone / toxicity
Wings, Animal / physiopathology
|
| IF |
2.985
|
| リソース情報 |
| ショウジョウバエ |
4349R-3
4963R-2 |
