TY  - JOUR
AU  - Bueno, Diones
AU  - Narayan Dey, Partha
AU  - Schacht, Teresa
AU  - Wolf, Christina
AU  - Wüllner, Verena
AU  - Morpurgo, Elena
AU  - Rojas-Charry, Liliana
AU  - Sessinghaus, Lena
AU  - Leukel, Petra
AU  - Sommer, Clemens
AU  - Radyushkin, Konstantin
AU  - Florin, Luise
AU  - Baumgart, Jan
AU  - Stamm, Paul
AU  - Daiber, Andreas
AU  - Horta, Guilherme
AU  - Nardi, Leonardo
AU  - Vasic, Verica
AU  - Schmeisser, Michael J.
AU  - Hellwig, Andrea
AU  - Oskamp, Angela
AU  - Bauer, Andreas
AU  - Anand, Ruchika
AU  - Reichert, Andreas S.
AU  - Ritz, Sandra
AU  - Nocera, Gianluigi
AU  - Jacob, Claire
AU  - Peper, Jonas
AU  - Silies, Marion
AU  - Frauenknecht, Katrin B. M.
AU  - Schäfer, Michael K. E.
AU  - Methner, Axel
TI  - NECAB2 is an endosomal protein important for striatal function
JO  - Free radical biology and medicine
VL  - 208
SN  - 0891-5849
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - FZJ-2023-03683
SP  - 643 - 656
PY  - 2023
N1  - Postprint liegt mir aktuell leider nicht vor
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 37722569
UR  - <Go to ISI:>//WOS:001083542200001
DO  - DOI:10.1016/j.freeradbiomed.2023.09.003
UR  - https://juser.fz-juelich.de/record/1015426
ER  -