PUMA- and Bax-induced autophagy contributes to apoptosis

Yee, K., Wilkinson, S., James, J., Ryan, K. and Vousden, K. (2009) PUMA- and Bax-induced autophagy contributes to apoptosis. Cell Death and Differentiation, 16(8), pp. 1135-1145. (doi: 10.1038/cdd.2009.28)

Abstract

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

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ryan, Professor Kevin and Yee, Dr Karen and Wilkinson, Dr Simon and Vousden, Karen
• Authors: Yee, K., Wilkinson, S., James, J., Ryan, K., and Vousden, K.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Cell Death and Differentiation
• ISSN: 1350-9047