PUMA- and Bax-induced autophagy contributes to apoptosis.
The p53-inducible BH3-only protein PUMA is a key mediator of p53-dependent apoptosis, and PUMA has been shown to function by activating Bax and mitochondrial outer membrane permeabilization. In this study, we describe an ability of PUMA to induce autophagy that leads to the selective removal of mitochondria. This function of PUMA depends on Bax/Bak and can be reproduced by overexpression of Bax. The induction of autophagy coincides with cytochrome c release, and taken together the results suggest that PUMA functions through Bax to induce mitochondrial autophagy in response to mitochondrial perturbations. Surprisingly, inhibition of PUMA or Bax-induced autophagy dampens the apoptotic response, suggesting that under some circumstances the selective targeting of mitochondria for autophagy can enhance apoptosis.
Yee
K S
KS
The Beatson Institute for Cancer Research, Garscube Estate, Glasgow, UK.
Wilkinson
S
S
James
J
J
Ryan
K M
KM
Vousden
K H
KH
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C477012:MAP1LC3A protein, human; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; C488588:PUMA protein, mouse; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c