The autophagy regulators Ambra1 and Beclin 1 are required for adult neurogenesis in the brain subventricular zone

• Published in: Cell death & disease 2014-09, Vol.5 (9), p.e1403-e1403
• Main Authors: Yazdankhah, M, Farioli-Vecchioli, S, Tonchev, A B, Stoykova, A, Cecconi, F
• Format: Article
• Language: English
• Subjects: 631/136/368/2431; 631/378/2183/2182; 631/80/82/39; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antibodies; Apoptosis Regulatory Proteins - deficiency; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Biochemistry; Biomedical and Life Sciences; Brain - metabolism; Brain - pathology; Cell Biology; Cell Culture; Cell Proliferation; Cells, Cultured; Heterozygote; Immunology; Lateral Ventricles - metabolism; Lateral Ventricles - pathology; Life Sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis; Original; original-article
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2014.358

Autophagy is a conserved proteolytic mechanism required for maintaining cellular homeostasis. The role of this process in vertebrate neural development is related to metabolic needs and stress responses, even though the importance of its progression has been observed in a number of circumstances, both in embryonic and in postnatal differentiating tissues. Here we show that the proautophagic proteins Ambra1 and Beclin 1, involved in the initial steps of autophagosome formation, are highly expressed in the adult subventricular zone (SVZ), whereas their downregulation in adult neural stem cells in vitro leads to a decrease in cell proliferation, an increase in basal apoptosis and an augmented sensitivity to DNA-damage-induced death. Further, Beclin 1 heterozygosis in vivo results in a significant reduction of proliferating cells and immature neurons in the SVZ, accompanied by a marked increase in apoptotic cell death. In sum, we propose that Ambra1- and Beclin 1-mediated autophagy plays a crucial role in adult neurogenesis, by controlling the survival of neural precursor cells.