title: Co-involvement of the mitochondria and endoplasmic reticulum in cell death induced by the novel ER-targeted protein HAP.
abstract: HAP (a homologue of the ASY/Nogo-B protein), a novel human apoptosis-inducing protein, was found to be identical to RTN3. In an earlier study, we demonstrated that HAP localized exclusively to the endoplasmic reticulum (ER) and that its overexpression could induce cell apoptosis via a depletion of endoplasmic reticulum (ER) Ca(2+) stores. In this study, we show that overexpression of HAP causes the activation of caspase-12 and caspase-3. We still detected the collapse of mitochondrial membrane potential (Deltaomegam) and the release of cytochrome c in HAP-overexpressing HeLa cells. All the results indicate that both the mitochondria and the ER are involved in apoptosis caused by HAP overexpression, and suggest that HAP overexpression may initiate an ER overload response (EOR) and bring about the downstream apoptotic events.
authors.affiliation: State Key Laboratory of Virology, Section of Molecular Virology, College of Life Sciences, Wuhan University, Wuhan, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Qi
mesh_terms: D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism*; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D002522:Chlorocebus aethiops; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C476198:RTN3 protein, human; D045304:Cytochromes c; D053454:Caspase 12; D053148:Caspase 3