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Examining BCL-2 Family Function with Large Unilamellar Vesicles
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Published on: October 5, 2012

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BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy

Lisa M Lindqvist1, David L Vaux1

  • 1Cell Signalling and Cell Death Division; Walter and Eliza Hall Institute of Medical Research; Melbourne, Victoria Australia; Department of Medical Biology; University of Melbourne; Parkville, Victoria Australia.

Autophagy
|July 4, 2014
PubMed

Insights

Prosurvival BCL2 family proteins do not directly regulate autophagy. Instead, they indirectly influence autophagy by inhibiting the activation of BAX and BAK1, key proteins in apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Regulation
  • Apoptosis Pathways

Background:

  • Prosurvival BCL2 family members are known to inhibit apoptosis.
  • These proteins are also thought to directly inhibit autophagy by binding to BECN1/Beclin 1.
  • The precise mechanism by which BCL2 family members affect autophagy remains unclear.

Purpose of the Study:

  • To determine if BCL2, BCL2L1/BCL-XL, or MCL1 directly or indirectly influence autophagy.
  • To differentiate between direct effects on autophagy versus indirect effects mediated by apoptosis inhibition.

Main Methods:

  • Comparison of normal cells with cells lacking BAX and BAK1.
  • Inhibition and overexpression of endogenous prosurvival BCL2 family members (BCL2, BCL2L1, MCL1).
  • Assessment of autophagy markers: LC3B lipidation, LC3B turnover, and autolysosome formation.

Main Results:

  • In cells capable of apoptosis, inhibiting prosurvival BCL2 proteins induced both autophagy and cell death.
  • In cells lacking BAX and BAK1 (unable to undergo apoptosis), manipulating BCL2 family proteins had no effect on autophagy markers.
  • LC3B lipidation, LC3B turnover, and autolysosome formation were unaffected by BCL2, BCL2L1, or MCL1 modulation in BAX/BAK1-deleted cells.

Conclusions:

  • Prosurvival BCL2 family members do not directly regulate autophagy.
  • Their influence on autophagy is indirect, mediated solely through the inhibition of BAX and BAK1 activation.
  • This finding clarifies the relationship between apoptosis and autophagy regulation by the BCL2 family.
Keywords:
BAK1BAXBCL-XLBCL2BCL2L1BECN1Beclin 1LC3BMCL1apoptosisautophagy

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