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Examining BCL-2 Family Function with Large Unilamellar Vesicles
08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

Necrosis-like death can engage multiple pro-apoptotic Bcl-2 protein family members

Denise Tischner1, Claudia Manzl1, Claudia Soratroi1

  • 1Division of Developmental Immunology, Biocenter, Medical University Innsbruck, 6020 Innsbruck, Austria.

Apoptosis : an International Journal on Programmed Cell Death
|September 14, 2012
PubMed

Insights

Necroptosis, a programmed cell death, involves unknown executioners. This study reveals mitochondrial involvement and cross-talk with apoptosis pathways in necroptosis, independent of caspases.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Immunology

Background:

  • Necroptosis is a regulated form of necrosis with known triggers but poorly understood execution mechanisms.
  • Investigating the molecular players and pathways involved in necroptosis is crucial for understanding cell death and disease.

Purpose of the Study:

  • To elucidate the executioners and signaling pathways of necrostatin-1 (Nec-1) sensitive necroptosis induced by various stimuli.
  • To explore the potential cross-talk between necroptosis and apoptosis, particularly involving mitochondrial pathways.

Main Methods:

  • Utilized L929 mouse fibrosarcoma cells, mouse embryonic fibroblasts (MEF), and bone marrow-derived macrophages.
  • Administered necroptosis inducers like TNFα, zVAD, and cadmium (Cd).
  • Assessed cell death mechanisms, including caspase independence, mitochondrial cytochrome c release, and involvement of proteins like Bmf, Bid, Bak, Bax, and PARP-2.

Main Results:

  • TNFα- or zVAD-induced necroptosis involved Bid and Bak, showed mitochondrial cytochrome c release, and was partly sensitive to cyclosporine A, suggesting mitochondrial permeability transition pore involvement.
  • Cadmium-induced necroptosis in L929 cells was Nec-1 sensitive, caspase-independent, and involved autocrine TNFα signaling.
  • Cadmium in MEFs induced mixed cell death, partly Nec-1 sensitive and involving Bmf and Bax/Bak, but remained caspase-insensitive.

Conclusions:

  • Both extrinsic and intrinsic necroptosis inducers can activate TNF-receptor signaling.
  • Necroptosis execution may involve mitochondrial alterations and proteins typically associated with apoptosis (e.g., Bax/Bak), leading to caspase-independent cell death.

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