| First Author | Barsukova AG | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 34 |
| Issue | 3 | Pages | 437-47 |
| PubMed ID | 21722208 | Mgi Jnum | J:177939 |
| Mgi Id | MGI:5296716 | Doi | 10.1111/j.1460-9568.2011.07760.x |
| Citation | Barsukova AG, et al. (2011) Mitochondrial calcium and its regulation in neurodegeneration induced by oxidative stress. Eur J Neurosci 34(3):437-47 |
| abstractText | A proposed mechanism of neuronal death associated with a variety of neurodegenerative diseases is the response of neurons to oxidative stress and consequent cytosolic Ca(2+) overload. One hypothesis is that cytosolic Ca(2+) overload leads to mitochondrial Ca(2+) overload and prolonged opening of the permeability transition pore (PTP), resulting in mitochondrial dysfunction. Elimination of cyclophilin D (CyPD), a key regulator of the PTP, results in neuroprotection in a number of murine models of neurodegeneration in which oxidative stress and high cytosolic Ca(2+) have been implicated. However, the effects of oxidative stress on the interplay between cytosolic and mitochondrial Ca(2+) in adult neurons and the role of the CyPD-dependent PTP in these dynamic processes have not been examined. Here, using primary cultured cerebral cortical neurons from adult wild-type (WT) mice and mice missing cyclophilin D (CyPD-KO), we directly assess cytosolic and mitochondrial Ca(2+) , as well as ATP levels, during oxidative stress. Our data demonstrate that during acute oxidative stress mitochondria contribute to neuronal Ca(2+) overload by release of their Ca(2+) stores. This result contrasts with the prevailing view of mitochondria as a buffer of cytosolic Ca(2+) under stress conditions. In addition, we show that CyPD deficiency reverses the release of mitochondrial Ca(2+) , leading to lower of cytosolic Ca(2+) levels, attenuation of the decrease in cytosolic and mitochondrial ATP, and a significantly higher viability of adult CyPD-knockout neurons following exposure of neurons oxidative stress. The study offers a first insight into the mechanism underlying CyPD-dependent neuroprotection during oxidative stress. |
