title: Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases.
abstract: Accumulating evidence indicate physiological significance of mitochondrial dynamics such as mitochondrial fusion and division, the dynamic movement of mitochondria along microtubules and interaction of mitochondria with the endoplasmic reticulum. A disruption in mitochondrial dynamics leads to a functional deterioration of mitochondria, resulting in a variety of diseases including neurodegenerative disorders. We previously identified a mitochondrial ubiquitin ligase MITOL/MARCH5, which belongs to the membrane-associated RING-CH E3 ubiquitin ligase (MARCH) family (also called MARCH5). MITOL plays an important role in the regulation of mitochondrial dynamics including mitochondrial morphology, transport and interaction with ER, at least in part, through the ubiquitinations of mitochondrial fission factor Drp1, microtubule-associated protein 1B and mitofusin2, respectively. This review focuses on recent findings that show how MITOL regulates mitochondrial dynamics and which suggest physiological disorders resulting from a failure in such regulation.
authors.affiliation: Laboratory of Molecular Biochemistry, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1, Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Nagashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokuyama
authors.forename: Ryo
authors.initials: R
authors.lastname: Yonashiro
authors.forename: Ryoko
authors.initials: R
authors.lastname: Inatome
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yanagi
mesh_terms: D000818:Animals; D034281:Dynamins; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D011489:Protein Denaturation; D017382:Reactive Oxygen Species / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C515578:MARCHF5 protein, human; D044767:Ubiquitin-Protein Ligases; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human; C110768:DNM1L protein, human; D034281:Dynamins
keywords: MAM; MAP1B; S-nitrosylation; mitochondrial dynamics; ubiquitin ligase