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Translocation of Bax and Bid to mitochondria, endoplasmic reticulum and nuclear envelope: possible control points in

Barbara Gajkowska1, Urszula Wojewódzka, Joanna Gajda

  • 1Laboratory of Cell Ultrastructure, Medical Research Centre, Polish Academy of Sciences, 5 Pawiński Street, 02 106 Warsaw, Poland.

Journal of Molecular Histology
|August 25, 2004
PubMed

Insights

Camptothecin induces breast cancer cell death by disrupting endoplasmic reticulum (ER) and mitochondria communication. This involves protein translocation, leading to calcium dysregulation and cytochrome c release, key events in apoptosis.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • The endoplasmic reticulum (ER) and mitochondria are crucial organelles involved in cellular homeostasis and apoptosis.
  • Cross-talk between ER and mitochondria plays a significant role in regulating calcium signaling and cell death pathways.
  • Dysfunctional ER-mitochondria communication is implicated in various diseases, including cancer.

Purpose of the Study:

  • To investigate the ER-mitochondria cross-talk during apoptosis in MCF-7 breast cancer cells.
  • To elucidate the role of camptothecin, a topoisomerase I inhibitor, in modulating ER-mitochondria interactions.
  • To examine the translocation of apoptotic proteins Bax and Bid and their impact on calcium homeostasis.

Main Methods:

  • Utilized MCF-7 breast cancer cell line.
  • Administered camptothecin to induce apoptosis.
  • Employed ultrastructural morphological, immunocytochemical, and histochemical techniques for electron microscopy.
  • Performed immunoelectron microscopy to localize Bax and Bid proteins.

Main Results:

  • Camptothecin induced early alterations in ER configuration and ER-mitochondria communication.
  • Bax and Bid proteins translocated from the cytoplasm to mitochondria, initiating mitochondrial dysfunction and cytochrome c release.
  • Bax and Bid were also detected in the ER and nuclear envelope, suggesting their involvement in calcium regulation.

Conclusions:

  • Camptothecin-induced apoptosis involves significant ER-mitochondria cross-talk disruption.
  • Bax and Bid mediate ER calcium depletion, leading to mitochondrial calcium overload and cytochrome c release.
  • Targeting ER-mitochondria calcium signaling presents a potential therapeutic strategy for breast cancer treatment.

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