7p0o | pdb_00007p0o
mitoNEET bound to M1 molecule
Structural highlights
FunctionCISD1_HUMAN Plays a key role in regulating maximal capacity for electron transport and oxidative phosphorylation (By similarity). May be involved in Fe-S cluster shuttling and/or in redox reactions.[1] [2] Publication Abstract from PubMedElevated 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. An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.,Marjault HB, Karmi O, Zuo K, Michaeli D, Eisenberg-Domovich Y, Rossetti G, de Chassey B, Vonderscher J, Cabantchik I, Carloni P, Mittler R, Livnah O, Meldrum E, Nechushtai R Commun Biol. 2022 May 10;5(1):437. doi: 10.1038/s42003-022-03393-x. PMID:35538231[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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