Mitochondrial Targets for Pharmacological Intervention in Human Disease

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Mitochondrial Targets for Pharmacological Intervention in Human Disease

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Title: Mitochondrial Targets for Pharmacological Intervention in Human Disease
Author: Malty, Ramy H.; Jessulat, Matthew; Jin, Ke; Musso, Gabriel; Vlasblom, James; Phanse, Sadhna; Zhang, Zhaolei; Babu, Mohan

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Citation: Malty, Ramy H., Matthew Jessulat, Ke Jin, Gabriel Musso, James Vlasblom, Sadhna Phanse, Zhaolei Zhang, and Mohan Babu. 2014. “Mitochondrial Targets for Pharmacological Intervention in Human Disease.” Journal of Proteome Research 14 (1): 5-21. doi:10.1021/pr500813f. http://dx.doi.org/10.1021/pr500813f.
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Abstract: Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function.
Published Version: doi:10.1021/pr500813f
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286170/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845191
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