Nutrient-Deprivation Autophagy Factor-1 (NAF-1): Biochemical Properties of a Novel Cellular Target for Anti-Diabetic Drugs

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Article on nutrient-deprivation autophagy factor-1 (NAF-1) and biochemical properties of a novel cellular target for anti-diabetic drugs.

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7 p. : col. ill.

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Tamir, Sagi; Zuris, John A.; Agranat, Lily; Lipper, Colin H.; Conlan, Andrea R.; Michaeli, Dorit et al. May 22, 2013.

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Article on nutrient-deprivation autophagy factor-1 (NAF-1) and biochemical properties of a novel cellular target for anti-diabetic drugs.

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7 p. : col. ill.

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Abstract: Nutrient-deprivation autophagy factor-1 (NAF-1) (synonyms: Cisd2, Eris, Miner1, and Noxp70) is a [2Fe-2S] cluster protein immune-detected both in endoplasmic reticulum (ER) and mitochondrial outer membrane. It was implicated in human pathology (Wolfram Syndrome 2) and in BCL-2 mediated antagonization of Beclin 1-dependent autophagy and depression of ER calcium stores. To gain insights about NAF-1 functions, we investigated the biochemical properties of its 2Fe-2S cluster and sensitivity of those properties to small molecules. The structure of the soluble domain of NAF-1 shows that it forms a homodimer with each protomer containing a [2Fe-2S] cluster bound by 3 Cys and one His. NAF-1 has shown the unusual abilities to transfer its 2Fe-2S cluster to an apo-acceptor protein (followed in vitro by spectrophotometry and by native PAGE electrophoresis) and to transfer iron to intact mitochondria in cell models (monitored by fluorescence imaging with iron fluorescent sensors targeted to mitochondria). Importantly, the drug pioglitazone abrogates NAF-1's ability to transfer the cluster to acceptor proteins and iron to mitochondria. Similar effects were found for the anti-diabetes and longevity-promoting antioxidant resveratrol. These results reveal NAF-1 as a previously unidentified cell target of anti-diabetes thiazolidinedione drugs like pioglitazone and of the natural product resveratrol, both of which interact with the protein and stabilize its labile [2Fe-2S] cluster.

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  • PLoS One, 2013, San Francisco: Public Library of Science

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  • Publication Title: PLoS One
  • Volume: 8
  • Issue: 5
  • Pages: 7
  • Peer Reviewed: Yes

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UNT Scholarly Works

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  • December 11, 2012

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  • March 7, 2013

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  • May 22, 2013

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  • Aug. 29, 2014, 2:16 p.m.

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Tamir, Sagi; Zuris, John A.; Agranat, Lily; Lipper, Colin H.; Conlan, Andrea R.; Michaeli, Dorit et al. Nutrient-Deprivation Autophagy Factor-1 (NAF-1): Biochemical Properties of a Novel Cellular Target for Anti-Diabetic Drugs, article, May 22, 2013; [San Francisco, California]. (digital.library.unt.edu/ark:/67531/metadc333047/: accessed September 19, 2017), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.