The Intriguing mitoNEET: Functional and Spectroscopic Properties of a Unique [2Fe-2S] Cluster Coordination Geometry

Despite the number of cellular and pathological mitoNEET-related processes, very few details are known about the mechanism of action of the protein. The recently discovered existence of a link between NEET proteins and cancer pave the way to consider mitoNEET and its Fe-S clusters as suitable targets to inhibit cancer cell proliferation. Here, we will review the variety of spectroscopic techniques that have been applied to study mitoNEET in an attempt to explain the drastic difference in clusters stability and reactivity observed for the two redox states, and to elucidate the cellular function of the protein. In particular, the extensive NMR assignment and the characterization of first coordination sphere provide a molecular fingerprint helpful to assist the design of drugs able to impair cellular processes or to directly participate in redox reactions or protein-protein recognition mechanisms.

Automated summary

Despite limited knowledge about the mechanism of mitoNEET protein, its link to cancer suggests that targeting mitoNEET and its Fe-S clusters could inhibit cancer cell proliferation. Spectroscopic techniques, such as NMR, have been used to study mitoNEET and understand the differences in cluster stability and reactivity, as well as its cellular function. NMR assignment and characterization of the first coordination sphere can aid in drug design to interfere with cellular processes or participate in redox reactions or protein-protein recognition mechanisms.