An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters

Henri Baptiste Marjault, Ola Karmi, Ke Zuo, Dorit Michaeli, Yael Eisenberg-Domovich, Giulia Rossetti, Benoit de Chassey, Jacky Vonderscher, Ioav Cabantchik, Paolo Carloni, Ron Mittler, Oded Livnah, Eric Meldrum, Rachel Nechushtai

Research output: Contribution to journalArticlepeer-review

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.

Original languageAmerican English
Article number437
JournalCommunications Biology
Volume5
Issue number1
DOIs
StatePublished - 10 May 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • Medicine (miscellaneous)

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