title: 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.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Germain
authors.forename: Angela P
authors.initials: AP
authors.lastname: Nguyen
authors.forename: J Nicole
authors.initials: JN
authors.lastname: Le Grand
authors.forename: Nicole
authors.initials: N
authors.lastname: Arbour
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: Vanderluit
authors.forename: David S
authors.initials: DS
authors.lastname: Park
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Opferman
authors.forename: Ruth S
authors.initials: RS
authors.lastname: Slack
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009474:Neurons / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C579094:Mcl1 protein, mouse; D008565:Membrane Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein