@article {Karmi2021,
	title = {A combined drug treatment that reduces mitochondrial iron and reactive oxygen levels recovers insulin secretion in NAF-1-deficient pancreatic cells},
	journal = {Antioxidants},
	volume = {10},
	number = {8},
	year = {2021},
	note = {cited By 9},
	abstract = {Decreased insulin secretion, associated with pancreatic β-cell failure, plays a critical role in many human diseases including diabetes, obesity, and cancer. While numerous studies linked β-cell failure with enhanced levels of reactive oxygen species (ROS), the development of diabetes associated with hereditary conditions that result in iron overload, e.g., hemochromatosis, Friedreich{\textquoteright}s ataxia, and Wolfram syndrome type 2 (WFS-T2; a mutation in CISD2, encoding the [2Fe-2S] protein NAF-1), underscores an additional link between iron metabolism and β-cell failure. Here, using NAF-1-repressed INS-1E pancreatic cells, we observed that NAF-1 repression inhibited insulin se-cretion, as well as impaired mitochondrial and ER structure and function. Importantly, we found that a combined treatment with the cell permeant iron chelator deferiprone and the glutathione precursor N-acetyl cysteine promoted the structural repair of mitochondria and ER, decreased mi-tochondrial labile iron and ROS levels, and restored glucose-stimulated insulin secretion. Addition-ally, treatment with the ferroptosis inhibitor ferrostatin-1 decreased cellular ROS formation and improved cellular growth of NAF-1 repressed pancreatic cells. Our findings reveal that suppressed expression of NAF-1 is associated with the development of ferroptosis-like features in pancreatic cells, and that reducing the levels of mitochondrial iron and ROS levels could be used as a therapeutic avenue for WFS-T2 patients. {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.},
	doi = {10.3390/antiox10081160},
	url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85110732792\&doi=10.3390\%2fantiox10081160\&partnerID=40\&md5=aa6b73bbcc14e9de504f030bc28b1949},
	author = {Karmi, O. and Sohn, Y.-S. and Marjault, H.-B. and Israeli, T. and Leibowitz, G. and Ioannidis, K. and Nahmias, Y. and Mittler, R. and Cabantchik, I.Z. and Nechushtai, R.}
}
