mitoNEET as a novel drug target for mitochondrial dysfunction

•Mitochondrial dysfunction plays an important part in several diseases.•mitoNEET is a mitochondrial protein that regulates bioenergetics in cells.•mitoNEET ligands to date are mainly thiazolidinediones based on pioglitazone.•mitoNEET ligands can be used to treat neurodegeneration or breast cancers.•This drug target opens up novel avenues for new treatment options in big pharma. Mitochondrial dysfunction plays an important part in the pathology of several diseases, including Alzheimer's disease and Parkinson's disease. Targeting mitochondrial proteins shows promise in treating and attenuating the neurodegeneration seen in these diseases, especially considering their complex and pleiotropic origins. Recently, the mitochondrial protein mitoNEET [also referred to as CDGSH iron sulfur domain 1 (CISD1)] has emerged as the mitochondrial target of thiazolidinedione drugs such as the antidiabetic pioglitazone. In this review, we evaluate the current understanding regarding how mitoNEET regulates cellular bioenergetics as well as the structural requirements for drug compound association with mitoNEET. With a clear understanding of mitoNEET function, it might be possible to develop therapeutic agents useful in several different diseases including neurodegeneration, breast cancer, diabetes and inflammation.