Historical Background
E3 ubiquitin ligases are a large family of proteins that recognize target substrates and mediate the transfer of ubiquitin from the E2 ubiquitin-conjugating enzyme to the substrate. These modifications can have diverse effects on the substrate, ranging from proteasome-dependent degradation to modulation of protein function, including activation and/or localization. The activity of most E3 ubiquitin ligases is specified by a RING domain, which is a protein structural domain of the zinc finger type containing a C3HC4amino acid motif. The mitochondrial ubiquitin ligase MITOL/MARCH5 belongs to the membrane-associated MARCH family of E3 ubiquitin ligases, which were originally discovered as structural homologs to Kaposi’s sarcoma-associated herpesvirus K3 and K5 ubiquitin E3 ligases. Hereafter, the term “MITOL” is used consistently when referring to this protein. MITOL is an...
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Gu H, Li Q, Huang S, Lu W, Cheng F, Gao P, et al. Mitochondrial E3 ligase March5 maintains stemness of mouse ES cells via suppression of ERK signalling. Nat Commun. 2015;6:7112. https://doi.org/10.1038/ncomms8112.
Merkwirth C, Langer T. Mitofusin 2 builds a bridge between ER and mitochondria. Cell. 2008;135:1165–7. https://doi.org/10.1016/j.cell.2008.12.005.
Nagashima S, Tokuyama T, Yonashiro R, Inatome R, Yanagi S. Roles of mitochondrial ubiquitin ligase MITOL/MARCH5 in mitochondrial dynamics and diseases. J Biochem. 2014;155:273–9. https://doi.org/10.1093/jb/mvu016.
Nakamura N, Kimura Y, Tokuda M, Honda S, Hirose S. MARCH-V is a novel mitofusin 2- and Drp1-binding protein able to change mitochondrial morphology. EMBO Rep. 2006;(7):1019–22. https://doi.org/10.1038/sj.embor.7400790.
Park YY, Lee S, Karbowski M, Neutzner A, Youle RJ, Cho H. Loss of MARCH5 mitochondrial E3 ubiquitin ligase induces cellular senescence through dynamin-related protein 1 and mitofusin 1. J Cell Sci. 2010;123:619–26. https://doi.org/10.1242/jcs.061481.
Shi HX, Liu X, Wang Q, Tang PP, Liu XY, Shan YF, et al. Mitochondrial ubiquitin ligase MARCH5 promotes TLR7 signaling by attenuating TANK action. PLoS Pathog. 2011;7:e1002057. https://doi.org/10.1371/journal.ppat.1002057.
Stroissnigg H, Trancikova A, Descovich L, Fuhrmann J, Kutschera W, Kostan J, et al. S-nitrosylation of microtubule-associated protein 1B mediates nitric-oxide-induced axon retraction. Nat Cell Biol. 2007;9:1035–45. https://doi.org/10.1038/ncb1625.
Sugiura A, Yonashiro R, Fukuda T, Matsushita N, Nagashima S, Inatome R, et al. A mitochondrial ubiquitin ligase MITOL controls cell toxicity of polyglutamine-expanded protein. Mitochondrion. 2011;11:139–46. https://doi.org/10.1016/j.mito.2010.09.001.
Sugiura A, Nagashima S, Tokuyama T, Amo T, Matsuki Y, Ishido S, et al. MITOL regulates endoplasmic reticulum-mitochondria contacts via mitofusin2. Mol Cell. 2013;51:20–34. https://doi.org/10.1016/j.molcel.2013.04.023.
Wang J, Aung LH, Prabhakar BS, Li P. The mitochondrial ubiquitin ligase plays an anti-apoptotic role in cardiomyocytes by regulating mitochondrial fission. J Cell Mol Med. 2016. https://doi.org/10.1111/jcmm.12914.
Xu S, Cherok E, Das S, Li S, Roelofs BA, Ge SX, et al. Mitochondrial E3 ubiquitin ligase MARCH5 controls mitochondrial fission and cell sensitivity to stress-induced apoptosis through regulation of MiD49 protein. Mol Biol Cell. 2016;27:349–59. https://doi.org/10.1091/mbc.E15-09-0678.
Yonashiro R, Ishido S, Kyo S, Fukuda T, Goto E, Matsuki Y, et al. A novel mitochondrial ubiquitin ligase plays a critical role in mitochondrial dynamics. EMBO J. 2006;25:3618–26.
Yonashiro R, Sugiura A, Miyachi M, Fukuda T, Matsushita N, Inatome R, et al. Mitochondrial ubiquitin ligase MITOL ubiquitinates mutant SOD1 and attenuates mutant SOD1-induced ROS generation. Mol Biol Cell. 2009;20:4254–530. https://doi.org/10.1091/mbc.E09-02-0112.
Yonashiro R, Kimijima Y, Shimura T, Kawaguchi K, Fukuda T, Inatome R, et al. Mitochondrial ubiquitin ligase MITOL blocks S-nitrosylated MAP1B–light chain 1-mediated mitochondrial dysfunction and neuronal cell death. Proc Natl Acad Sci USA. 2012;109:2382–7. https://doi.org/10.1073/pnas.1114985109.
Yoo YS, Park YY, Kim JH, Cho H, Kim SH, Lee HS, et al. The mitochondrial ubiquitin ligase MARCH5 resolves MAVS aggregates during antiviral signalling. Nat Commun. 2015;6:7910. https://doi.org/10.1038/ncomms8910.
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Tokuyama, T., Yanagi, S. (2018). Mitochondrial Ubiquitin Ligase MITOL/MARCH5. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101579
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101579
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