Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1

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Updated: Aug 22, 2026

Intracellular Refolding Assay
07:18

Intracellular Refolding Assay

Published on: January 24, 2012

Rohan Steel1, Judith P Doherty, Katherine Buzzard

  • 1Peter MacCallum Cancer Centre, A'Beckett St., Locked Bag #1, Melbourne, Victoria 8006, Australia.

The Journal of Biological Chemistry
|September 17, 2004
PubMed

Insights

Heat shock protein 72 (Hsp72) prevents apoptosis by blocking mitochondrial cytochrome c release during cellular stress. Its protective effects occur before mitochondria are damaged, not by inhibiting the apoptosome.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Heat shock proteins (HSPs) are crucial for cellular protection against various stresses.
  • Hsp72 is known to play a role in preventing apoptosis, a key cellular process.
  • Previous studies suggested Hsp72 inhibits apoptosis by interfering with apoptosome formation.

Purpose of the Study:

  • To investigate the precise mechanism by which Hsp72 protects cells from apoptosis.
  • To determine the critical point at which Hsp72 exerts its protective effects.
  • To clarify the interaction of Hsp72 with the apoptotic pathway, specifically the apoptosome.

Main Methods:

  • Simultaneous measurement of cytochrome c localization and nuclear morphology in mouse embryo fibroblasts.
  • Assessment of Hsp72's effect on apoptosis induction following cytotoxic stress.
  • Evaluation of recombinant Hsp72's impact on caspase activity in cytosolic extracts.
  • Analysis of the role of salt concentration in Hsp72 preparations on apoptosome inhibition.

Main Results:

  • Hsp72 effectively blocks cytochrome c release from mitochondria, preventing apoptosis initiation.
  • The permeabilization of the outer mitochondrial membrane is identified as the critical cellular event.
  • Hsp72 does not inhibit apoptosis once cytochrome c has been released.
  • Apparent inhibition of caspase activation by recombinant Hsp72 was attributed to high salt content in the preparation, not Hsp72 itself.
  • Hsp72 did not inhibit cytochrome c-stimulated caspase activity in cellular extracts.

Conclusions:

  • The protective mechanism of Hsp72 against apoptosis operates upstream of mitochondrial damage.
  • Hsp72 prevents the release of cytochrome c from mitochondria, thereby safeguarding cells.
  • Hsp72 does not inhibit the apoptosome or downstream caspase activation; its role is pre-mitochondrial release.

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