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Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes
Author(s) -
Annis Ryan P.,
Swahari Vijay,
Nakamura Ayumi,
Xie Alison X.,
Hammond Scott M.,
Deshmukh Mohanish
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13944
Subject(s) - apoptosis , biology , microrna , microbiology and biotechnology , downregulation and upregulation , neuron , nervous system , neuroscience , central nervous system , programmed cell death , gene , genetics
Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR‐29 family of micro RNA s (mi RNA s) are induced with neuronal maturation and that overexpression of miR‐29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR‐29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR‐29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR‐29‐deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR‐24 as another mi RNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR‐29 by targeting a similar repertoire of prodeath BH 3‐only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long‐term survival.