Preprint

FZJ-2023-00602

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png NECAB2 participates in an endosomal pathway of mitochondrial stress response at striatal synapses

Bueno, D. ; Dey, P. N. ; Schacht, T. ; Wolf, C. ; Wüllner, V. ; Morpurgo, E. ; Rojas-Charry, L. ; Sessinghaus, L. ; Leukel, P. ; Sommer, C. ; Radyushkin, K. ; Schäfer, M. K. E. ; Florin, L. ; Gomez-Zepeda, D. ; Tenzer, S. ; Baumgart, J. ; Stamm, P. ; Daiber, A. ; Horta, G. ; Nardi, L. ; Vasic, V. ; Schmeisser, M. J. ; Hellwig, A. ; Oskamp, A.FZJ* ; Bauer, A.FZJ* ; Anand, R. ; Reichert, A. ; Ritz, S. ; Peper, J. ; Silies, M. ; Frauenknecht, K. B. M. ; Methner, A.

2021
Cold Spring Harbor Laboratory, NY Cold Spring Harbor

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Please use a persistent id in citations: http://hdl.handle.net/2128/33587  doi:10.1101/2021.02.15.431234

Abstract: Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control and repair. We found that global knockout of the neuronal calcium-binding protein 2 (NECAB2) in the mouse causes loss of striatal synapses and behavioral phenotypes related to striatal dysfunction such as reduced motivation and altered sensory gating. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller. They are characterized by increased respiration and superoxide production resulting in oxidative stress. This accumulation of dysfunctional mitochondria is caused by a defective assembly of mitochondria with early endosomes in a pathway that involves the small GTPase Rab5 and its guanine nucleotide exchange factor Alsin/ALS2. NECAB2 therefore participates in an endosomal pathway of mitochondrial stress response and repair important for striatal function.

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Contributing Institute(s):

1. Molekulare Organisation des Gehirns (INM-2)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2022

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Database coverage:

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