Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes. (18th November 2016)

• Record Type: Journal Article
• Authors: Annis, Ryan P.; Swahari, Vijay; Nakamura, Ayumi; Xie, Alison X.; Hammond, Scott M.; Deshmukh, Mohanish
• Is Part Of: FEBS journal. Volume 283:Number 24(2016)
• Page Start: 4569
• Page End: 4582
• Publication Date: 2016-11-18
• Subjects: apoptosis -- maturation -- miR‐24 -- miR‐29 -- neurons; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13944
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : 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 microRNAs (miRNAs) 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 miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR‐29 by targeting a similar repertoire of prodeath BH3‐only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long‐term survival. Abstract : Sympathetic neurons are known to transition from a state where they are acutely sensitive to apoptosis early in development to a state where apoptosis is restricted as they mature. Here we report that mature neurons induce the microRNA miR‐24, which can act redundantly with the previously identified antiapoptotic microRNA miR‐29 by inhibiting a similar set of proapoptotic BH3‐only genes.