Histone H2AX promotes neuronal health by controlling mitochondrial homeostasis
| Autor: | Bindu D. Paul, Urbain Weyemi, Adarsha P. Malla, Maged M. Harraz, Deeya Bhattacharya, William M. Bonner, Solomon H. Snyder, Myriem Boufraqech |
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| Rok vydání: | 2019 |
| Předmět: |
Programmed cell death
Oxidative phosphorylation Biology Mitochondrion environment and public health Neuroprotection Oxidative Phosphorylation Electron Transport Histones Mice Neural Stem Cells Animals Phosphorylation Mice Knockout Neurons Multidisciplinary Cell Death Biological Sciences Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria Cell biology enzymes and coenzymes (carbohydrates) Mitochondrial biogenesis Knockout mouse Ectopic expression biological phenomena cell phenomena and immunity |
| Zdroj: | Proceedings of the National Academy of Sciences. 116:7471-7476 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1820245116 |
| Popis: | Phosphorylation of histone H2AX is a major contributor to efficient DNA repair. We recently reported neurobehavioral deficits in mice lacking H2AX. Here we establish that this neural failure stems from impairment of mitochondrial function and repression of the mitochondrial biogenesis gene PGC-1α. H2AX loss leads to reduced levels of the major subunits of the mitochondrial respiratory complexes in mouse embryonic fibroblasts and in the striatum, a brain region particularly vulnerable to mitochondrial damage. These defects are substantiated by disruption of the mitochondrial shape in H2AX mutant cells. Ectopic expression of PGC-1α restores mitochondrial oxidative phosphorylation complexes and mitigates cell death. H2AX knockout mice display increased neuronal death in the brain when challenged with 3-nitropronionic acid, which targets mitochondria. This study establishes a role for H2AX in mitochondrial homeostasis associated with neuroprotection. |
| Databáze: | OpenAIRE |
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