holinger jbc 274, 13298-304, 1999 stapled alpha-helix of bcl-2 domains (sahb) walensky science 305,...
TRANSCRIPT
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Holinger JBC 274, 13298-304, 1999
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Stapled alpha-helix of BCL-2 domains (SAHB)
Walensky Science 305, 1466-70, 2004
Proposed mechanism of bcl-2 pore formation
Gottlob et al., Genes Dev 2001
Akt inhibits Bax/Bak activation (Majewski, Mol Cell Biol
2004)
Bid displaces mitochondrial hexokinase (ibid)
Conditions leading to loss of mitochondrial hexokinase induce apoptosis even in Bax/Bak -/- cells, and are rescued by Akt, but not Bcl-2 (Majewski, Mol Cell 2004)
QuickTime™ and aTIFF (Uncompressed) decompressor
are needed to see this picture.
Copyright ©2005 American Society for Clinical Investigation
Levine, B. et al. J. Clin. Invest. 2005;115:2679-2688
The autophagy pathway and its role in cellular adaptation to nutrient deprivation
Copyright ©2005 American Society for Clinical Investigation
Levine, B. et al. J. Clin. Invest. 2005;115:2679-2688
The molecular mechanisms of autophagy
Copyright ©2005 American Society for Clinical Investigation
Levine, B. et al. J. Clin. Invest. 2005;115:2679-2688
Ultrastructural examples of apoptotic and autophagic cell death
Lum et al., 2005
Shimizu et al., Nat Cell Biol 2004
Autophagy is a response to nutrient stress to maintain adequate internal levels of nutrients(self-cannabilization).
Role in cell death is best revealed if apoptosis is disabled (bax/bak-/-, caspase inhibitors, Bcl-xL++).
In nutrient-poor conditions (or equivalent effects on mTOR signaling), autophagy maintains survival.
In nutrient-rich conditions, autophagy promotes cell death in response to other types of stress.