NEET Proteins: A New Link Between Iron Metabolism, Reactive Oxygen Species, and Cancer.

Abstract

SIGNIFICANCE:

Cancer cells accumulate high levels of iron and reactive oxygen species (ROS) to promote their high metabolic activity and proliferation rate. However, high levels of iron and ROS can also lead to enhanced oxidative stress and the activation of cell death pathways such as apoptosis and ferroptosis. This has led to the proposal that different drugs that target iron and/or ROS metabolism could be used as anticancer drugs. However, due to the complex role iron and ROS play in cells, the majority of these drugs yielded mixed results, highlighting a critical need to identify new players in the regulation of iron and ROS homeostasis in cancer cells. Recent Advances: NEET proteins belong to a newly discovered class of iron-sulfur proteins (2Fe-2S) required for the regulation of iron and ROS homeostasis in cells. Recent studies revealed that the NEET proteins NAF-1 (CISD2) and mitoNEET (CISD1) play a critical role in promoting the proliferation of cancer cells, supporting tumor growth and metastasis. Moreover, the function of NEET proteins in cancer cells was found to be dependent of the degree of lability of their 2Fe-2S clusters.

CRITICAL ISSUES:

NEET proteins could represent a key regulatory link between the maintenance of high iron and ROS in cancer cells, the activation of cell death and survival pathways, and cellular proliferation.

FUTURE DIRECTIONS:

Because the function of NEET proteins depends on the lability of their clusters, drugs that target the 2Fe2S clusters of NEET proteins could be used as promising anticancer drugs.

• Authors: Ron Mittler, Merav Darash-Yahana, Yang Sung Sohn, Fang Bai, Luhua Song, Ioav Z Cabantchik, Patricia A Jennings, José N Onuchic, Rachel Nechushtai
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 30 Issue 8 Pg. 1083-1095 (03 10 2019) ISSN: 1557-7716 [Electronic] United States
• PMID: 29463105 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)

Chemical References

• CISD1 protein, human
• CISD2 protein, human
• Iron-Sulfur Proteins
• Membrane Proteins
• Mitochondrial Proteins
• Reactive Oxygen Species
• Iron

Topics

• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Homeostasis
• Humans
• Iron (metabolism)
• Iron-Sulfur Proteins (metabolism)
• Membrane Proteins (metabolism)
• Mitochondrial Proteins (metabolism)
• Neoplasm Metastasis
• Neoplasms (metabolism)
• Reactive Oxygen Species (metabolism)