Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration

Han Zhang, Yun wu Zhang, Yaomin Chen, Xiumei Huang, Fangfang Zhou, Weiwei Wang, Bo Xian, Xian Zhang, Eliezer Masliah, Quan Chen, Jing Dong J. Han, Guojun Bu, John C. Reed, Francesca Fang Liao, Ye Guang Chen, Huaxi Xu

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Apoptosis is an essential cellular process in multiple diseases and a major pathway for neuronal death in neurodegeneration. The detailed signaling events/pathways leading to apoptosis, especially in neurons, require further elucidation. Here we identify a β-amyloid precursor protein (APP)-interacting protein, designated as appoptosin, whose levels are upregulated in brain samples from Alzheimer's disease and infarct patients, and in rodent stroke models, as well as in neurons treated with β-amyloid (Aβ) and glutamate. We further demonstrate that appoptosin induces reactive oxygen species release and intrinsic caspase-dependent apoptosis. The physiological function of appoptosin is to transport/exchange glycine/5-amino-levulinic acid across the mitochondrial membrane for heme synthesis. Downregulation of appoptosin prevents cell death and caspase activation caused by glutamate or Aβ insults. APP modulates appoptosin-mediated apoptosis through interaction with appoptosin. Our study identifies appoptosin as a crucial player in apoptosis and a novel pro-apoptotic protein involved in neuronal cell death, providing a possible new therapeutic target for neurodegenerative disorders.

Original languageEnglish (US)
Pages (from-to)15565-15576
Number of pages12
JournalJournal of Neuroscience
Volume32
Issue number44
DOIs
StatePublished - Oct 31 2012

    Fingerprint

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, H., Zhang, Y. W., Chen, Y., Huang, X., Zhou, F., Wang, W., Xian, B., Zhang, X., Masliah, E., Chen, Q., Han, J. D. J., Bu, G., Reed, J. C., Liao, F. F., Chen, Y. G., & Xu, H. (2012). Appoptosin is a novel pro-apoptotic protein and mediates cell death in neurodegeneration. Journal of Neuroscience, 32(44), 15565-15576. https://doi.org/10.1523/JNEUROSCI.3668-12.2012