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Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, \u03b1-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their \u03b1-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway.<\/jats:p>","DOI":"10.1091\/mbc.11.5.1919","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T23:51:59Z","timestamp":1372809119000},"page":"1919-1932","source":"Crossref","is-referenced-by-count":103,"title":["Branched Chain Amino Acids Induce Apoptosis in Neural Cells without Mitochondrial Membrane Depolarization or Cytochrome<i>c<\/i>Release: Implications for Neurological Impairment Associated with Maple Syrup Urine Disease"],"prefix":"10.1091","volume":"11","author":[{"given":"Philippe","family":"Jouvet","sequence":"first","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Rustin","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherches sur les Handicaps G\u00e9n\u00e9tiques de l'Enfant, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U393, H\u00f4pital Necker Enfants Malades, 75743 Paris Cedex 15, France; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna L.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Pocock","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Institute of Neurology, University College London, London WC1N 1PJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Felderhoff-Mueser","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Mazarakis","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sarraf","sequence":"additional","affiliation":[{"name":"Division of Investigative Sciences, Imperial College of Science, Technology, and Medicine, Hammersmith Hospital, London W12 0NN, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umesh","family":"Joashi","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Kozma","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Greenwood","sequence":"additional","affiliation":[{"name":"Weston Laboratory, Division of Paediatrics, Obstetrics, and Gynaecology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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