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We tested the hypothesis that this neuronal apoptosis is initiated by oxidative stress and the mitochondrial permeability transition pore (mPTP). Preapoptotic LGN neurons accumulate mitochondria, Zn<jats:sup>2+<\/jats:sup>and Ca<jats:sup>2+<\/jats:sup>, and generate higher levels of reactive oxygen species (ROS), including superoxide, nitric oxide (NO), and peroxynitrite, than LGN neurons with an intact cortical target. Preapoptosis of LGN neurons is associated with increased formation of protein carbonyls, protein nitration, and protein<jats:italic>S<\/jats:italic>-nitrosylation. Genetic deletion of nitric oxide synthase 1 (<jats:italic>nos1<\/jats:italic>) and inhibition of NOS1 with nitroindazole protected LGN neurons from apoptosis, revealing NO as a mediator. Putative components of the mPTP are expressed in mouse LGN, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D (CyPD). Nitration of CyPD and ANT in LGN mitochondria occurs by 2 d after cortical injury. Chemical cross-linking showed that LGN neuron preapoptosis is associated with formation of CyPD and VDAC oligomers, consistent with mPTP formation. Mice without CyPD are rescued from neuron apoptosis as are mice treated with the mPTP inhibitors TRO-19622 (cholest-4-en-3-one oxime) and TAT-Bcl-X<jats:sub>L<\/jats:sub>-BH4. Manipulation of the mPTP markedly attenuated the early preapoptotic production of reactive oxygen\/nitrogen species in target-deprived neurons. Our results demonstrate in adult mouse brain neurons that the mPTP functions to enhance ROS production and the mPTP and NO trigger apoptosis; thus, the mPTP is a target for neuroprotection<jats:italic>in vivo<\/jats:italic>.<\/jats:p>","DOI":"10.1523\/jneurosci.2225-10.2011","type":"journal-article","created":{"date-parts":[[2011,1,5]],"date-time":"2011-01-05T17:27:57Z","timestamp":1294248477000},"page":"359-370","source":"Crossref","is-referenced-by-count":88,"title":["The Mitochondrial Permeability Transition Pore Regulates Nitric Oxide-Mediated Apoptosis of Neurons Induced by Target Deprivation"],"prefix":"10.1523","volume":"31","author":[{"given":"Lee J.","family":"Martin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal A.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2011,1,5]]},"reference":[{"key":"2023041303481025000_31.1.359.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65588-5"},{"key":"2023041303481025000_31.1.359.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00363-9"},{"key":"2023041303481025000_31.1.359.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(98)00014-1"},{"key":"2023041303481025000_31.1.359.4","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1523\/JNEUROSCI.16-05-01710.1996","article-title":"DNA damage and apoptosis in Alzheimer's disease: colocalization with c-Jun immunoreactivity, relationship to brain area, and effect of postmortem delay","volume":"16","author":"Anderson","year":"1996","journal-title":"J Neurosci"},{"key":"2023041303481025000_31.1.359.5","first-page":"25","article-title":"Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease","volume":"12","author":"Anglade","year":"1997","journal-title":"Histol Histopathol"},{"key":"2023041303481025000_31.1.359.6","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.370"},{"key":"2023041303481025000_31.1.359.7","doi-asserted-by":"crossref","first-page":"6908","DOI":"10.1523\/JNEUROSCI.17-18-06908.1997","article-title":"Mechanisms of reduced striatal MNDA excitotoxicity in type I nitric oxide synthase knock-out mice","volume":"17","author":"Ayata","year":"1997","journal-title":"J Neurosci"},{"key":"2023041303481025000_31.1.359.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature03434"},{"key":"2023041303481025000_31.1.359.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.001"},{"key":"2023041303481025000_31.1.359.10","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/00005072-197304000-00004","article-title":"Ultrastructure of retrograde degeneration in thalamus of rat. 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