%0 Journal Article
%A Marjault, Henri-Baptiste
%A Karmi, Ola
%A Zuo, Ke
%A Michaeli, Dorit
%A Eisenberg-Domovich, Yael
%A Rossetti, Giulia
%A de Chassey, Benoit
%A Vonderscher, Jacky
%A Cabantchik, Ioav
%A Carloni, Paolo
%A Mittler, Ron
%A Livnah, Oded
%A Meldrum, Eric
%A Nechushtai, Rachel
%T An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters
%J Communications biology
%V 5
%N 1
%@ 2399-3642
%C London
%I Springer Nature
%M FZJ-2022-02136
%P 437
%D 2022
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:35538231
%U <Go to ISI:>//WOS:000793196800001
%R 10.1038/s42003-022-03393-x
%U https://juser.fz-juelich.de/record/907657