We have studied programmed cell death in the nervous system and the biochemical mechanism of apoptosis in general. (1) To analyze apoptosis in the nervous system we developed a new method to identify apoptotic cells under the microscope. This new method allowed us to identify apoptosis as the method of cerebellar granule cell death during development and after MPP+ treatment. (2) We have developed monoclonal antibodies against apoptosis regulatory proteins Bcl-2, Bcl-x, and Bax to probe their mechanism of action in vitro and in vivo. The antibodies reveal that Bax migrates from the cytosol to cell membranes during apoposis. (4) To explore Bax, Bcl-2 and Bcl-xl movement in neurons the green flourescent protein has been used to tag and follow the proteins during apoptosis. We discovered that Bax and Bcl-xl move from the cytosol to the mitochendria as an essential step in their mechanism of apoptosis control. (5) We found RNase L to mediate virus and interferon-induced apoptosis. (6) We developed a new way to block cell apoptosis by delivery of Bcl-x to the cell surface. - programmed cell death; nervous system; apoptosis; Bcl-2
| Tondera, Daniel; Grandemange, Stephanie; Jourdain, Alexis et al. (2009) SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J 28:1589-600 |
| Narendra, Derek; Tanaka, Atsushi; Suen, Der-Fen et al. (2009) Parkin-induced mitophagy in the pathogenesis of Parkinson disease. Autophagy 5:706-8 |
| Suen, Der-Fen; Norris, Kristi L; Youle, Richard J (2008) Mitochondrial dynamics and apoptosis. Genes Dev 22:1577-90 |
| Tanaka, Atsushi; Youle, Richard J (2008) A chemical inhibitor of DRP1 uncouples mitochondrial fission and apoptosis. Mol Cell 29:409-10 |
| Youle, Richard J; Strasser, Andreas (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47-59 |
| Norris, Kristi L; Youle, Richard J (2008) Cytomegalovirus proteins vMIA and m38.5 link mitochondrial morphogenesis to Bcl-2 family proteins. J Virol 82:6232-43 |
| Zanna, Claudia; Ghelli, Anna; Porcelli, Anna Maria et al. (2008) OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain 131:352-67 |
| Goyal, Gaurav; Fell, Brennan; Sarin, Apurva et al. (2007) Role of mitochondrial remodeling in programmed cell death in Drosophila melanogaster. Dev Cell 12:807-16 |
| Lee, Seungmin; Jeong, Seon-Yong; Lim, Won-Chung et al. (2007) Mitochondrial fission and fusion mediators, hFis1 and OPA1, modulate cellular senescence. J Biol Chem 282:22977-83 |
| Neutzner, Albert; Youle, Richard J; Karbowski, Mariusz (2007) Outer mitochondrial membrane protein degradation by the proteasome. Novartis Found Symp 287:4-14;discussion 14-20 |
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