| First Author | Barsukova A | Year | 2011 |
| Journal | Eur J Neurosci | Volume | 33 |
| Issue | 5 | Pages | 831-42 |
| PubMed ID | 21255127 | Mgi Jnum | J:176850 |
| Mgi Id | MGI:5292819 | Doi | 10.1111/j.1460-9568.2010.07576.x |
| Citation | Barsukova A, et al. (2011) Activation of the mitochondrial permeability transition pore modulates Ca2+ responses to physiological stimuli in adult neurons. Eur J Neurosci 33(5):831-42 |
| abstractText | The participation of mitochondria in cellular and neuronal Ca(2+) homeostatic networks is now well accepted. Yet, critical tests of specific mitochondrial pathways in neuronal Ca(2+) responses have been hampered because the identity of mitochondrial proteins that must be integrated within this dynamic system remain uncertain. One putative pathway for Ca(2+) efflux from mitochondria exists through the formation of the permeability transition pore (PTP) that is often associated with cellular and neuronal death. Here, we have evaluated neuronal Ca(2+) dynamics and the PTP in single adult neurons in wild-type mice and those missing cyclophilin D (CyPD), a key regulator of the PTP. Using high-resolution time-lapse imaging, we demonstrate that PTP opening only follows simultaneous activation with two physiological stimuli that generate critical threshold levels of cytosolic and mitochondrial Ca(2+) . Our results are the first to demonstrate CyPD-dependent PTP opening in normal neuronal Ca(2+) homeostatic mechanisms not leading to activation of cell death pathways. As neurons in mice lacking CyPD are protected in a number of neurodegenerative disease models, the results suggest that improved viability of CyPD-knockout animals in these pathological states may be due to the transient, rather than persistent, activation of the PTP in mutant mitochondria, thereby shielding neurons from cytoplasmic Ca(2+) overload. |
