The molecular machinery of mitochondrial fusion and fission: An opportunity for drug discovery?
The mitochondria form dynamic organized networks or filaments that are controlled by fusion and fission events. A balance between mitochondrial fusion and fission is crucial for the correct function of these organelles. Thus, a detailed characterization of the proteins involved in mitochondrial fusion and fission, and the study of the mechanisms that regulate these two processes, would contribute to elucidating how this balance is achieved. In this regard, alterations in some of the proteins that participate in mitochondrial dynamics are linked to human pathology. In addition, experimental data support the view that mitochondrial metabolism is regulated via the manipulation of the proteins involved in mitochondrial dynamics, particularly the mitofusin 2 protein. This review evaluates the potential of mitochondrial fusion and fission proteins as targets for drug discovery, with an emphasis on mitofusin 2. The pharmacological modulation of mitochondrial dynamics may be beneficial for the treatment of specific disorders of mitochondrial dynamics and mitochondrial-inherited diseases, as well as in complex diseases with a central mitochondrial dysfunction.
Zorzano
Antonio
A
Institute for Research in Biomedicine, Barcelona, Spain. antonio.zorzano@irbbarcelona.org
Sebastián
David
D
Segalés
Jessica
J
Palacín
Manuel
M
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002607:Charcot-Marie-Tooth Disease / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D015195:Drug Design; D055808:Drug Discovery; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects* / Q000235:genetics; D050576:Membrane Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000188:drug therapy / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D054928:Validation Studies as Topic
D050576:Membrane Fusion Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C488751:Mfn2 protein, mouse; C489710:Mfn2 protein, rat