Mitochondrial dynamics proteins as emerging drug targets |
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| Institution: | 1. Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA;2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA;3. Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA;4. Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, Bronx, NY, USA;5. Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY, USA;1. Aix Marseille Université, CNRS, INSERM, Institut Paoli-Calmettes, Centre de Recherche en Cancérologie de Marseille (CRCM), F-13009 Marseille, France;1. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA;1. Department of Pharmaceutical Sciences and Drug Discovery Center, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA;1. Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal;2. MedInUP – Center for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal;3. Department of Research, BIAL-Portela & Cª, S.A., Coronado, Portugal;4. Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Coimbra, Portugal;1. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK;1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA;2. Departments of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA |
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| Abstract: | The importance of mitochondrial dynamics, the physiological process of mitochondrial fusion and fission, in regulating diverse cellular functions and cellular fitness has been well established. Several pathologies are associated with aberrant mitochondrial fusion or fission that is often a consequence of deregulated mitochondrial dynamics proteins; however, pharmacological targeting of these proteins has been lacking and is challenged by complex molecular mechanisms. Recent studies have advanced our understanding in this area and have enabled rational drug design and chemical screening strategies. We provide an updated overview of the regulatory mechanisms of fusion and fission proteins, their structure–function relationships, and the discovery of pharmacological modulators demonstrating their therapeutic potential. These advances provide exciting opportunities for the development of prototype therapeutics for various diseases. |
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