Impact of pH on Bax alpha conformation, oligomerisation and mitochondrial integration

The change in the conformation of Bax at the onset of apoptosis is a determinant for the execution of this cell death programme. However, very few models can account for this modification and the factors involved in this process remain elusive. We have analysed the modifications in the conformation induced by a variation in pH using a cell-free assay. We show that a moderate basic or acidic pH can induce apoptotic-like changes in the conformation of Bax, such as the exposure of the N-terminal or the BH3 domain. These changes in the conformation are associated with the binding of Bax to mitochondria and an enhanced Bax homo- and oligomerisation. Our results suggest that variations in the pH, in a range consistent with that often observed during apoptosis, are sufficient to trigger Bax translocation to mitochondria and the subsequent release of apoptogenic factors from this organelle.