論文 - 詳細
| RRC ID | 64057 |
|---|---|
| 著者 | Chukai Y, Iwamoto T, Itoh K, Tomita H, Ozaki T. |
| タイトル | Characterization of mitochondrial calpain-5. |
| ジャーナル | Biochim Biophys Acta Mol Cell Res |
| Abstract |
Calpain, a Ca2+-dependent cysteine protease, plays a significant role in gene expression, signal transduction, and apoptosis. Mutations in human calpain-5 cause autosomal dominant neovascular inflammatory vitreoretinopathy and the inhibition of calpain-5 activity may constitute an effective therapeutic strategy for this condition. Although calpain-5 is ubiquitously expressed in mammalian tissues and was recently found to be present in the mitochondria as well as in the cytosol, its physiological function and enzymological properties require further elucidation. The objective of the current study was to determine the characteristics of mitochondrial calpain-5 in porcine retinas, human HeLa cells, and C57BL/6J mice using subcellular fractionation. We found that mitochondrial calpain-5 was proteolyzed/autolyzed at low Ca2+ concentrations in mitochondria isolated from porcine retinas and by thapsigargin-induced endoplasmic reticulum (ER) stress in HeLa cells. Further, mitochondrial calpain-5, as opposed to cytosolic calpain-5, was activated during the early stages of ER stress in C57BL/6J mice. These results showed that mitochondrial calpain-5 was activated at low Ca2+ concentrations in vitro and in response to ER stress in vivo. The present study provides new insights into a novel calpain system in the mitochondria that includes stress responses during the early phases of ER stress. Further, activation of mitochondrial calpain-5 by treatment using low-molecular-weight compounds may have therapeutic potential for diseases related to ER stress, including neurodegenerative diseases, metabolic syndromes, diabetes, and cancer. |
| 巻・号 | 1868(5) |
| ページ | 118989 |
| 公開日 | 2021-4-1 |
| DOI | 10.1016/j.bbamcr.2021.118989 |
| PII | S0167-4889(21)00043-4 |
| PMID | 33607190 |
| MeSH | Animals Calcium / metabolism* Calpain / metabolism* Cytosol / metabolism Endoplasmic Reticulum Stress Enzyme Activation HeLa Cells Humans Mice Mice, Inbred C57BL Mitochondria / metabolism Retina / metabolism* Swine |
| IF | 4.105 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | |
| ヒト・動物細胞 | HeLa(RCB0007) |