Characterization of mitochondrial calpain-5
| Autor: | Taku Ozaki, Takeshi Iwamoto, Ken Itoh, Hiroshi Tomita, Yusaku Chukai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Swine Mitochondrion Retina Mice 03 medical and health sciences Cytosol 0302 clinical medicine Animals Humans Molecular Biology biology Calpain Chemistry Endoplasmic reticulum Cell Biology Endoplasmic Reticulum Stress Cysteine protease Cell biology Mitochondria Enzyme Activation Mice Inbred C57BL 030104 developmental biology Liver Apoptosis 030220 oncology & carcinogenesis Calpain-5 Unfolded protein response biology.protein Calcium Signal transduction Autolysis ER stress HeLa Cells |
| Zdroj: | Biochimica et Biophysica Acta : Molecular Cell Research. 1868(5):118989 |
| ISSN: | 0167-4889 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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