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NECAB2 is an endosomal protein important for striatal function

Synaptic signaling depends on ATP generated by mitochondria. Dysfunctional mitochondria shift the redox balance towards a more oxidative environment. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction. We found that neuronal calcium-binding protein 2 (N...

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Main Authors: Bueno, Diones (Author) , Dey, Partha Narayan (Author) , Schacht, Teresa (Author) , Wolf, Christina (Author) , Wüllner, Verena (Author) , Morpurgo, Elena (Author) , Rojas-Charry, Liliana (Author) , Sessinghaus, Lena (Author) , Leukel, Petra (Author) , Sommer, Clemens (Author) , Radyushkin, Konstantin (Author) , Florin, Luise (Author) , Baumgart, Jan (Author) , Stamm, Paul (Author) , Daiber, Andreas (Author) , Horta, Guilherme Maria Chambino (Author) , Nardi, Leonardo (Author) , Vasic, Verica (Author) , Schmeißer, Michael Joachim (Author) , Hellwig, Andrea (Author) , Oskamp, Angela (Author) , Bauer, Andreas (Author) , Anand, Ruchika (Author) , Reichert, Andreas (Author) , Ritz, Sandra (Author) , Nocera, Gianluigi (Author) , Jacob, Claire (Author) , Peper, Jonas (Author) , Silies, Marion (Author) , Frauenknecht, Katrin Barbara Magda (Author) , Schäfer, Michael (Author) , Methner, Axel (Author)
Format: Article (Journal)
Language:English
Published: 1 November 2023
In: Free radical biology and medicine
Year: 2023, Volume: 208, Pages: 643-656
ISSN:1873-4596
DOI:10.1016/j.freeradbiomed.2023.09.003
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.freeradbiomed.2023.09.003
Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S0891584923006159
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Author Notes:Diones Bueno, Partha Narayan Dey, Teresa Schacht, Christina Wolf, Verena Wüllner, Elena Morpurgo, Liliana Rojas-Charry, Lena Sessinghaus, Petra Leukel, Clemens Sommer, Konstantin Radyushkin, Luise Florin, Jan Baumgart, Paul Stamm, Andreas Daiber, Guilherme Horta, Leonardo Nardi, Verica Vasic, Michael J. Schmeisser, Andrea Hellwig, Angela Oskamp, Andreas Bauer, Ruchika Anand, Andreas S. Reichert, Sandra Ritz, Gianluigi Nocera, Claire Jacob, Jonas Peper, Marion Silies, Katrin B.M. Frauenknecht, Michael K.E. Schäfer, Axel Methner
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Summary:Synaptic signaling depends on ATP generated by mitochondria. Dysfunctional mitochondria shift the redox balance towards a more oxidative environment. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction. We found that neuronal calcium-binding protein 2 (NECAB2) plays a role in striatal function and mitochondrial homeostasis. NECAB2 is a predominantly endosomal striatal protein which partially colocalizes with mitochondria. This colocalization is enhanced by mild oxidative stress. Global knockout of Necab2 in the mouse results in increased superoxide levels, increased DNA oxidation and reduced levels of the antioxidant glutathione which correlates with an altered mitochondrial shape and function. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller and characterized by a reduced spare capacity suggestive of intrinsic uncoupling respectively mitochondrial dysfunction. In line with this, we also found an altered stress-induced interaction of endosomes with mitochondria in Necab2 knockout striatal cultures. The predominance of dysfunctional mitochondria and the pro-oxidative redox milieu correlates with a loss of striatal synapses and behavioral changes characteristic of striatal dysfunction like reduced motivation and altered sensory gating. Together this suggests an involvement of NECAB2 in an endosomal pathway of mitochondrial stress response important for striatal function.
Item Description:Gesehen am 20.02.2024
Physical Description:Online Resource
ISSN:1873-4596
DOI:10.1016/j.freeradbiomed.2023.09.003

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