| Structural highlights
Function
CISD1_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 PubMed
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.
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
- ↑ Wiley SE, Paddock ML, Abresch EC, Gross L, van der Geer P, Nechushtai R, Murphy AN, Jennings PA, Dixon JE. The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster. J Biol Chem. 2007 Aug 17;282(33):23745-9. Epub 2007 Jun 21. PMID:17584744 doi:C700107200
- ↑ Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. PMID:17766440
- ↑ 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. An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters. Commun Biol. 2022 May 10;5(1):437. PMID:35538231 doi:10.1038/s42003-022-03393-x
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