Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1
| العنوان: | Decreased expression of Drp1 and Fis1 mediates mitochondrial elongation in senescent cells and enhances resistance to oxidative stress through PINK1 |
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| المؤلفون: | Jürgen Bereiter-Hahn, Marina Jendrach, Sören Mai, Georg Auburger, Michael Klinkenberg |
| المصدر: | Journal of Cell Science. 123:917-926 |
| بيانات النشر: | The Company of Biologists, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Dynamins, FIS1, Senescence, Umbilical Veins, endocrine system, Cell type, Light, PINK1, Mitochondrion, Biology, medicine.disease_cause, Models, Biological, Gene Expression Regulation, Enzymologic, GTP Phosphohydrolases, Mitochondrial Proteins, Downregulation and upregulation, medicine, Humans, RNA, Messenger, Cellular Senescence, Endothelial Cells, Membrane Proteins, Cell Biology, Mitochondria, Up-Regulation, Cell biology, Oxidative Stress, Mitochondrial fission, Reactive Oxygen Species, Microtubule-Associated Proteins, Protein Kinases, Oxidative stress |
| الوصف: | Mitochondria display different morphologies, depending on cell type and physiological situation. In many senescent cell types, an extensive elongation of mitochondria occurs, implying that the increase of mitochondrial length in senescence could have a functional role. To test this hypothesis, human endothelial cells (HUVECs) were aged in vitro. Young HUVECs had tubular mitochondria, whereas senescent cells were characterized by long interconnected mitochondria. The change in mitochondrial morphology was caused by downregulation of the expression of Fis1 and Drp1, two proteins regulating mitochondrial fission. Targeted photodamage of mitochondria induced the formation of reactive oxygen species (ROS), which triggered mitochondrial fragmentation and loss of membrane potential in young cells, whereas senescent cells proved to be resistant. Alterations of the Fis1 and Drp1 expression levels also influenced the expression of the putative serine-threonine kinase PINK1, which is associated with the PARK6 variant of Parkinson's disease. Downregulation of PINK1 or overexpression of a PINK1 mutant (G309D) increased the sensitivity against ROS in young cells. These results indicate that there is a Drp1- and Fis1-induced, and PINK1-mediated protection mechanism in senescent cells, which, when compromised, could contribute to the age-related progression of Parkinson's disease and arteriosclerosis. |
| تدمد: | 1477-9137 0021-9533 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ad74df911841ecb979b2b0a45dc2d8a8Test https://doi.org/10.1242/jcs.059246Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ad74df911841ecb979b2b0a45dc2d8a8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779137 00219533 |
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