Journal Article

FZJ-2022-02136

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters

Marjault, H.-B. ; Karmi, O. ; Zuo, K. ; Michaeli, D. ; Eisenberg-Domovich, Y. ; Rossetti, G.FZJ* ; de Chassey, B. ; Vonderscher, J. ; Cabantchik, I. ; Carloni, P.FZJ* ; Mittler, R. ; Livnah, O. ; Meldrum, E. ; Nechushtai, R. (Corresponding author)

2022
Springer Nature London

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Please use a persistent id in citations: http://hdl.handle.net/2128/31192  doi:10.1038/s42003-022-03393-x

Abstract: Elevated levels of mitochondrial iron and reactive oxygen species (ROS) accompany the progression of diabetes, negatively impacting insulin production and secretion from pancreatic cells. In search for a tool to reduce mitochondrial iron and ROS levels, we arrived at a molecule that destabilizes the [2Fe-2S] clusters of NEET proteins (M1). Treatment of db/db diabetic mice with M1 improved hyperglycemia, without the weight gain observed with alternative treatments such as rosiglitazone. The molecular interactions of M1 with the NEET proteins mNT and NAF-1 were determined by X-crystallography. The possibility of controlling diabetes by molecules that destabilize the [2Fe–2S] clusters of NEET proteins, thereby reducing iron-mediated oxidative stress, opens a new route for managing metabolic aberration such as in diabetes.

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Contributing Institute(s):

1. Computational Biomedicine (IAS-5)
2. Computational Biomedicine (INM-9)
3. Jülich Supercomputing Center (JSC)

Research Program(s):

1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)
2. 5111 - Domain-Specific Simulation & Data Life Cycle Labs (SDLs) and Research Groups (POF4-511) (POF4-511)

Appears in the scientific report 2022

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