title: Mature neurons dynamically restrict apoptosis via redundant premitochondrial brakes.
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.
authors: Neuroscience Center, UNC Chapel Hill, NC, USA.|Curriculum in Neurobiology, UNC Chapel Hill, NC, USA.
authors: Ryan P
authors: RP
authors: Annis
authors: Neuroscience Center, UNC Chapel Hill, NC, USA.
authors: Vijay
authors: V
authors: Swahari
authors: Neuroscience Center, UNC Chapel Hill, NC, USA.|Curriculum in Neurobiology, UNC Chapel Hill, NC, USA.
authors: Ayumi
authors: A
authors: Nakamura
authors: Department of Pharmacology, UNC Chapel Hill, NC, USA.
authors: Alison X
authors: AX
authors: Xie
authors: Department of Cell Biology and Physiology, UNC Chapel Hill, NC, USA.
authors: Scott M
authors: SM
authors: Hammond
authors: Neuroscience Center, UNC Chapel Hill, NC, USA.|Curriculum in Neurobiology, UNC Chapel Hill, NC, USA.|Department of Cell Biology and Physiology, UNC Chapel Hill, NC, USA.
authors: Mohanish
authors: M
authors: Deshmukh
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D005724:Ganglia / Q000166:cytology; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C529080:Mirn24 microRNA, mouse; C488588:PUMA protein, mouse; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D045304:Cytochromes c
keywords: apoptosis; maturation; miR-24; miR-29; neurons