MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner

Abstract

Apoptosis has an important role during development to regulate cell number. In differentiated cells, however, activation of autophagy has a critical role by enabling cells to remain functional following stress. In this study, we show that the antiapoptotic BCL‐2 homologue MCL‐1 has a key role in controlling both processes in a developmentally regulated manner. Specifically, MCL‐1 degradation is an early event not only following induction of apoptosis, but also under nutrient deprivation conditions where MCL‐1 levels regulate activation of autophagy. Furthermore, deletion of MCL‐1 in cortical neurons of transgenic mice activates a robust autophagic response. This autophagic response can, however, be converted to apoptosis by either reducing the levels of the autophagy regulator Beclin‐1, or by a concomitant activation of BAX. Our results define a pathway whereby MCL‐1 has a key role in determining cell fate, by coordinately regulating apoptosis and autophagy.