High glucose–induced ROS activates TRPM2 to trigger lysosomal membrane permeabilization and Zn 2+ -mediated mitochondrial fission
| Autor: | Jing Li, Asipu Sivaprasadarao, Tim S. Munsey, Lin-Hua Jiang, Nada Abuarab |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Reactive oxygen species Endothelium Cell Biology Mitochondrion Biology medicine.disease_cause Biochemistry Cell biology 03 medical and health sciences 030104 developmental biology medicine.anatomical_structure chemistry RNA interference medicine Mitochondrial fission TRPM2 Signal transduction Molecular Biology Oxidative stress |
| Zdroj: | Science Signaling. 10 |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.aal4161 |
| Popis: | Diabetic stress increases the production of reactive oxygen species (ROS), leading to mitochondrial fragmentation and dysfunction. We hypothesized that ROS-sensitive TRPM2 channels mediated diabetic stress-induced mitochondrial fragmentation. We found that chemical inhibitors, RNAi silencing, and genetic knockout of TRPM2 channels abolished the ability of high glucose to cause mitochondrial fission in endothelial cells, a cell type that is particularly vulnerable to diabetic stress. Similar to high glucose, increasing ROS in endothelial cells by applying H2O2 induced mitochondrial fission. Ca2+ that entered through TRPM2 induced lysosomal membrane permeabilization, which led to the release of lysosomal Zn2+ and a subsequent increase in mitochondrial Zn2+ Zn2+ promoted the recruitment of the fission factor Drp-1 to mitochondria to trigger their fission. This signaling pathway may operate in aging-associated illnesses in which excessive mitochondrial fragmentation plays a central role. |
| Databáze: | OpenAIRE |
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