A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration
| Autor: | Natalie Qishan Zhang, YT Cheung, Sally Shuk Yee Cheng, S Wuwongse, Simon Ming-Yuen Lee, Yuen Shan Ho, Raymond Chuen-Chung Chang, Clara Hiu-Ling Hung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry Aβ β-amyloid H2O2 Hydrogen peroxide Mitochondrion Biochemistry Mitochondrial apoptosis-induced channel Hippocampus Mitochondrial Dynamics Mito-RFP Mitochondria-targeted dsRed Rats Sprague-Dawley chemistry.chemical_compound Fission and fusion Mito-GFP Mitochondria-targeted green fluorescent protein Drp-1 lcsh:QH301-705.5 Cells Cultured chemistry.chemical_classification lcsh:R5-920 Mfn Mitofusin Microscopy Confocal Superoxide β-amyloid Caspase 3 OPA1 Optic atrophy 1 Neurodegeneration FCCP Carbonyl cyanide p-trifluoro-methoxy-phenyl-hydrazine Alzheimer's disease Cell biology Mitochondria mitochondrial fusion Drp1 Dynamin-related protein 1 Mitochondrial fission Female lcsh:Medicine (General) TMRE Tetramethylrhodamine ethyl ester Research Paper Mito-KillerRed KillerRed-dMito Biology AD Alzheimer’s disease 03 medical and health sciences ER Endoplasmic reticulum Rotenone medicine Animals Reactive oxygen species Amyloid beta-Peptides Organic Chemistry Hydrogen Peroxide Mito-PAGFP Photoactivable mitochondria-targeted green fluorescent protein medicine.disease Rats 030104 developmental biology lcsh:Biology (General) Mitochondrial permeability transition pore chemistry Mff Mitochondrial fission factor SPA-FRAP Simultaneous photoactivation and fluorescence recovery after photobleaching Reactive Oxygen Species ER-RFP Endoplasmic reticulum-targeted dsRed ROS Reactive oxygen species |
| Zdroj: | Redox Biology Redox Biology, Vol 14, Iss, Pp 7-19 (2018) |
| ISSN: | 2213-2317 |
| Popis: | Mitochondrial fragmentation due to fission/fusion imbalance has often been linked to mitochondrial dysfunction and apoptosis in neurodegeneration. Conventionally, it is believed that once mitochondrial morphology shifts away from its physiological tubular form, mitochondria become defective and downstream apoptotic signaling pathways are triggered. However, our study shows that beta-amyloid (Aβ) induces morphological changes in mitochondria where they become granular-shaped and are distinct from fragmented mitochondria in terms of both morphology and functions. Accumulation of mitochondrial reactive oxygen species triggers granular mitochondria formation, while mitoTEMPO (a mitochondria-targeted superoxide scavenger) restores tubular mitochondrial morphology within Aβ-treated neurons. Interestingly, modulations of mitochondria fission and fusion by genetic and pharmacological tools attenuated not only the induction of granular mitochondria, but also mitochondrial superoxide levels in Aβ−treated neurons. Our study shows a reciprocal relationship between mitochondrial dynamics and reactive oxygen species and provides a new potential therapeutic target at early stages of neurodegenerative disease pathogenesis. Graphical abstract fx1 Highlights • Aβ induces granular mitochondria at early stages of neurodegeneration. • Mitochondrial ROS triggers aberrant mitochondrial dynamics & granular mitochondria. • Granular mitochondria is reversible and attenuated by mitoTEMPO. • Manipulation of mitochondrial dynamics abolishes formation of granular mitochondria, but also reduces super oxide levels in mitochondria. • Manipulation of mitochondrial dynamics reduces super oxide levels in mitochondria. |
| Databáze: | OpenAIRE |
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