title: Principles of the mitochondrial fusion and fission cycle in neurons.
abstract: Mitochondrial fusion-fission dynamics play a crucial role in many important cell processes. These dynamics control mitochondrial morphology, which in turn influences several important mitochondrial properties including mitochondrial bioenergetics and quality control, and they appear to be affected in several neurodegenerative diseases. However, an integrated and quantitative understanding of how fusion-fission dynamics control mitochondrial morphology has not yet been described. Here, we took advantage of modern visualisation techniques to provide a clear explanation of how fusion and fission correlate with mitochondrial length and motility in neurons. Our main findings demonstrate that: (1) the probability of a single mitochondrion splitting is determined by its length; (2) the probability of a single mitochondrion fusing is determined primarily by its motility; (3) the fusion and fission cycle is driven by changes in mitochondrial length and deviations from this cycle serves as a corrective mechanism to avoid extreme mitochondrial length; (4) impaired mitochondrial motility in neurons overexpressing 120Q Htt or Tau suppresses mitochondrial fusion and leads to mitochondrial shortening whereas stimulation of mitochondrial motility by overexpressing Miro-1 restores mitochondrial fusion rates and sizes. Taken together, our results provide a novel insight into the complex crosstalk between different processes involved in mitochondrial dynamics. This knowledge will increase understanding of the dynamic mitochondrial functions in cells and in particular, the pathogenesis of mitochondrial-related neurodegenerative diseases.
authors.affiliation: Department of Pharmacology, Centre of Excellence for Translational Medicine, University of Tartu, Ravila 19, Tartu, Estonia.
authors.forename: Michal
authors.initials: M
authors.lastname: Cagalinec
authors.forename: Dzhamilja
authors.initials: D
authors.lastname: Safiulina
authors.forename: Mailis
authors.initials: M
authors.lastname: Liiv
authors.forename: Joanna
authors.initials: J
authors.lastname: Liiv
authors.forename: Vinay
authors.initials: V
authors.lastname: Choubey
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Wareski
authors.forename: Vladimir
authors.initials: V
authors.lastname: Veksler
authors.forename: Allen
authors.initials: A
authors.lastname: Kaasik
mesh_terms: D000818:Animals; D006801:Humans; D000071058:Huntingtin Protein; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D053142:Mitochondrial Size / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D009474:Neurons / Q000648:ultrastructure*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D019076:Transgenes / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D016875:tau Proteins; C473124:RHOT1 protein, human; D020741:rho GTP-Binding Proteins
keywords: Mitochondrial dynamics; Mitochondrial fusion; Neurodegeneration; Neurons