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

doi:10.1038/s42003-022-03393-x

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

The Hebrew University of Jerusalem

Research output: Contribution to journal › Article › peer-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 language	English
Article number	437
Journal	Communications Biology
Volume	5
Issue number	1
DOIs	https://doi.org/10.1038/s42003-022-03393-x
State	Published - 10 May 2022

All Science Journal Classification (ASJC) codes

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s42003-022-03393-x

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Marjault, H. B., 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. (2022). An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters. Communications Biology, 5(1), Article 437. https://doi.org/10.1038/s42003-022-03393-x

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

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.",

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

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doi = "10.1038/s42003-022-03393-x",

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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 2022, 'An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters', Communications Biology, vol. 5, no. 1, 437. https://doi.org/10.1038/s42003-022-03393-x

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T1 - An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters

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

PY - 2022/5/10

Y1 - 2022/5/10

N2 - 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.

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.

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DO - 10.1038/s42003-022-03393-x

M3 - مقالة

C2 - 35538231

SN - 2399-3642

VL - 5

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 437

ER -

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

Abstract

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