論文 - 詳細
| RRC ID | 47421 |
|---|---|
| 著者 | Qi Y, Liu H, Daniels MP, Zhang G, Xu H. |
| タイトル | Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration. |
| ジャーナル | Cell Death Differ |
| Abstract |
Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency. |
| 巻・号 | 23(2) |
| ページ | 291-302 |
| 公開日 | 2016-2-1 |
| DOI | 10.1038/cdd.2015.94 |
| PII | cdd201594 |
| PMID | 26160069 |
| PMC | PMC4716308 |
| MeSH | Animals Apoptosis* Cell Line Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster Gene Knockout Techniques Male Metalloendopeptidases / genetics* Metalloendopeptidases / metabolism Mitochondria / enzymology* Mitochondria / pathology Nerve Degeneration / enzymology* Reactive Oxygen Species / metabolism Unfolded Protein Response |
| IF | 10.717 |
| 引用数 | 17 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ショウジョウバエ | |