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

Abstract	In 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.
Authors	Kevin B Clayton, Petar Podlesniy, Joana Figueiro-Silva, Guillermo López-Doménech, Lluis Benitez, Marta Enguita, Maria A Abad, Eduardo Soriano, Ramon Trullas
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 32 Issue 4 Pg. 1453-66 (Jan 25 2012) ISSN: 1529-2401 [Electronic] United States
PMID	22279230 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Bax protein, mouse Nerve Tissue Proteins bcl-2-Associated X Protein neuronal pentraxin C-Reactive Protein
Topics	Animals Animals, Newborn C-Reactive Protein (physiology) Cells, Cultured Female HEK293 Cells Humans Male Mice Mice, 129 Strain Mice, Knockout Mitochondria (metabolism) Molecular Dynamics Simulation Nerve Tissue Proteins (physiology) Neurons (metabolism) Rats Rats, Sprague-Dawley bcl-2-Associated X Protein (metabolism)

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