BCL-2 homologues lie at the interface between apoptosis and autophagy, regulating these two critical cellular
pathways. However, the mechanisms controlling their coordinate regulation and the consequences on cellular
survival are not fully understood. We recently showed that MCL-1 is a critical regulator of autophagy in cell lines
and neurons. Our findings indicate that activation of apoptosis and autophagy is controlled in a developmentally
regulated manner. In addition, the fact that MCL-1 null neurons die in an autophagy-dependent manner suggests that while a basal level of autophagy is required for neuronal survival, its sustained activation may be detrimental. This could have major implications for the treatment of neurodegenerative diseases using strategies involving activation of autophagy to clear protein aggregates from the brain.
M Germain, AP Nguyen, Grand JN Le, N Arbour, JL Vanderluit, DS Park, JT Opferman, RS Slack. MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. EMBO J 2011; 30: 395- 407.
PMID: 21245831 DOI: 10.1038/emboj.2010.3