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Title

NP1 regulates neuronal activity-dependent accumulation of BAX in mitochondria and mitochondrial dynamics

AuthorsClayton, Kevin B. ; Podlesniy, Petar ; Figueiro-Silva, Joana ; Benítez, Lluís ; Enguita, Marta ; Trullas, Ramón
Issue Date2012
PublisherSociety for Neuroscience
CitationJournal of Neuroscience 32(4): 1453-1466 (2012)
AbstractIn cultured cerebellar granule neurons, low neuronal activity triggers the intrinsic program of apoptosis, which requires protein synthesis-dependent BAX translocation to mitochondria, a process that may underlie neuronal damage in neurodegeneration. However, the mechanisms that link neuronal activity with the induction of the mitochondrial program of apoptosis remain unclear. Neuronal pentraxin 1 (NP1) is a pro-apoptotic protein induced by low neuronal activity that is increased in damaged neurites in Alzheimer's disease-affected brains. Here we report that NP1 facilitates the accumulation of BAX in mitochondria and regulates mitochondrial dynamics during apoptosis in rat and mouse cerebellar granule neurons in culture. Reduction of neuronal activity increases NP1 protein levels in mitochondria and contributes to mitochondrial fragmentation in a Bax-dependent manner. In addition, NP1 is involved in mitochondrial transport in healthy neurons. These results show that NP1 is targeted to mitochondria acting upstream of BAX and uncover a novel function for NP1 in the regulation of mitochondrial dynamics and trafficking during apoptotic neurodegeneration. © 2012 the authors.
DescriptionNeurobiology of Disease.-- et al.
Publisher version (URL)http://dx.doi.org/10.1523/JNEUROSCI.4604-11.2012
URIhttp://hdl.handle.net/10261/73728
DOI10.1523/JNEUROSCI.4604-11.2012
Identifiersdoi: 10.1523/JNEUROSCI.4604-11.2012
issn: 0270-6474
Appears in Collections:(IIBB) Artículos
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