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Co-involvement of the mitochondria and endoplasmic reticulum in cell death induced by the novel ertargeted protein HAP

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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) Ca2+ 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 (Δωm) 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.

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Correspondence to Yi-Peng Qi.

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Key words

  • Apoptosis-inducing protein HAP
  • Mitochondria
  • Endoplasmic reticulum (ER)
  • Caspase-12
  • Caspase-3
  • Mitochondrial membrane potential (Δωm)
  • Cytochrome c