TY  - JOUR
AU  - Marjault, Henri-Baptiste
AU  - Karmi, Ola
AU  - Zuo, Ke
AU  - Michaeli, Dorit
AU  - Eisenberg-Domovich, Yael
AU  - Rossetti, Giulia
AU  - de Chassey, Benoit
AU  - Vonderscher, Jacky
AU  - Cabantchik, Ioav
AU  - Carloni, Paolo
AU  - Mittler, Ron
AU  - Livnah, Oded
AU  - Meldrum, Eric
AU  - Nechushtai, Rachel
TI  - An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters
JO  - Communications biology
VL  - 5
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - FZJ-2022-02136
SP  - 437
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:35538231
UR  - <Go to ISI:>//WOS:000793196800001
DO  - DOI:10.1038/s42003-022-03393-x
UR  - https://juser.fz-juelich.de/record/907657
ER  -