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Holinger JBC 274, 13298-304, 1999

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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)

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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.