Authors:	van der Kooij, Michael A. Rojas-Charry, Liliana Givehchi, Maryam Wolf, Christina Bueno, Diones Arndt, Sabine Tenzer, Stefan Mattioni, Lorenzo Treccani, Giulia Hasch, Annika Schmeisser, Michael J. Vianello, Caterina Giacomello, Marta Methner, Axel
Title:	Chronic social stress disrupts the intracellular redistribution of brain hexokinase 3 induced by shifts in peripheral glucose levels
Online publication date:	30-Jan-2023
Year of first publication:	2022
Language:	english
Abstract:	Chronic stress has the potential to impair health and may increase the vulnerability for psychiatric disorders. Emerging evidence suggests that specific neurometabolic dysfunctions play a role herein. In mice, chronic social defeat (CSD) stress reduces cerebral glucose uptake despite hyperglycemia. We hypothesized that this metabolic decoupling would be reflected by changes in contact sites between mitochondria and the endoplasmic reticulum, important intracellular nutrient sensors, and signaling hubs. We thus analyzed the proteome of their biochemical counterparts, mitochondria-associated membranes (MAMs) from whole brain tissue obtained from CSD and control mice. This revealed a lack of the glucose-metabolizing enzyme hexokinase 3 (HK3) in MAMs from CSD mice. In controls, HK3 protein abundance in MAMs and also in striatal synaptosomes correlated positively with peripheral blood glucose levels, but this connection was lost in CSD. We conclude that the ability of HK3 to traffic to sites of need, such as MAMs or synapses, is abolished upon CSD and surmise that this contributes to a cellular dysfunction instigated by chronic stress.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-8295
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Journal of molecular medicine 100
Pages or article number:	1441 1453
Publisher:	Springer
Publisher place:	Berlin u.a.
Issue date:	2022
ISSN:	1432-1440
Publisher DOI:	10.1007/s00109-022-02235-x
Appears in collections:	DFG-491381577-H