OPA1 haploinsufficiency due to a novel splicing variant resulting in mitochondrial dysfunction without mitochondrial DNA depletion

References

• Skidd PM, Lessell S, Cestari DM. 2013. Autosomal dominant hereditary optic neuropathy (ADOA): a review of the genetics and clinical manifestations of ADOA and ADOA+. Semin Ophthalmol. 28(5–6):422–26. doi:10.3109/08820538.2013.825296.
   PubMed Web of Science ®Google Scholar
• Yu‐Wai‐Man P, Votruba M, Burté F, La Morgia C, Barboni P, Carelli V. 2016. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathol. 132(6):789–806. doi:10.1007/s00401-016-1625-2.
   PubMed Web of Science ®Google Scholar
• Del Dotto V, Fogazza M, Carelli V, Rugolo M, Zanna C. Eight human OPA1isoforms, long and short: what are they for? Biochim Biophys Acta Bioenerg. 2018; 1859(4):263–69. doi:10.1016/j.bbabio.2018.01.005.
   PubMed Web of Science ®Google Scholar
• Pesch UE, Leo-Kottler B, Mayer S, Jurklies B, Kellner U, Apfelstedt-Sylla E, Zrenner E, Alexander C, Wissinger B. 2001. OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum Mol Genet. 10(13):1359–68. doi:10.1093/hmg/10.13.1359.
   PubMed Web of Science ®Google Scholar
• Zanna C, Ghelli A, Porcelli AM, Karbowski M, Youle RJ, Schimpf S, Wissinger B, Pinti M, Cossarizza A, Vidoni S, et al. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain. 2008;131(Pt 2):352–67. doi:10.1093/brain/awm335.
   PubMed Web of Science ®Google Scholar
• Elachouri G, Vidoni S, Zanna C, Pattyn A, Boukhaddaoui H, Gaget K, Yu-Wai-Man P, Gasparre G, Sarzi E, Delettre C, et al. OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Res. 2011;21(1):12–20. doi:10.1101/gr.108696.110.
   PubMed Web of Science ®Google Scholar
• Song Z, Chen H, Fiket M, Alexander C, Chan DC. 2007. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J Cell Biol. 178(5):749–55. doi:10.1083/jcb.200704110.
   PubMed Web of Science ®Google Scholar
• Kane MS, Alban J, Desquiret-Dumas V, Gueguen N, Ishak L, Ferre M, Amati-Bonneau P, Procaccio V, Bonneau D, Lenaers G, et al. 2017. Autophagy controls the pathogenicity of OPA1 mutations in dominant optic atrophy. J Cell Mol Med. 21(10):2284–97. doi:10.1111/jcmm.13149.
   PubMed Web of Science ®Google Scholar
• Li H, Jones EM, Li H, Yang L, Sun Z, Yuan Z, Chen R, Dong F, Sui R. 2018. Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy pedigrees with six novel OPA1 pathogenic variants. Ophthalmic Genet. 39(5):569–76. doi:10.1080/13816810.2018.1466337.
   PubMed Web of Science ®Google Scholar
• Bolognini R, Gerth-Kahlert C, Abegg M, Bartholdi D, Mathis N, Sturm V, Gallati S, Schaller A. 2017. Characterization of two novel intronic OPA1 mutations resulting in aberrant pre-mRNA splicing. BMC Med Genet. 18(1):22. doi:10.1186/s12881-017-0383-x.
   PubMed Web of Science ®Google Scholar
• Miller G, Lipman M. Release of infectious Epstein-Barr virus by transformed marmoset leukocytes. Proc Natl Acad Sci USA. 1973;70:190–94. doi:10.1073/pnas.70.1.190.
   PubMed Web of Science ®Google Scholar
• Yu J, Xiao Y, Liu J, Ji Y, Liu H, Xu J, Jin X, Liu L, Guan MX, Jiang P. 2014. Loss of MED1 triggers mitochondrial biogenesis in C2C12 cells. Mitochondrion. 14(1):18–25. doi:10.1016/j.mito.2013.12.004.
   PubMed Web of Science ®Google Scholar
• Zhao X, Han J, Zhu L, Xiao Y, Wang C, Hong F, Jiang P, Guan MX. 2018. Overexpression of human mitochondrial alanyl-tRNA synthetase suppresses biochemical defects of the mt-tRNAAla mutation in cybrids. Int J Biol Sci. 14(11):1437–44. doi:10.7150/ijbs.27043.
   PubMed Web of Science ®Google Scholar
• Kim JY, Hwang JM, Ko HS, Seong MW, Park BJ, Park SS. 2005. Mitochondrial DNA content is decreased in autosomal dominant optic atrophy. Neurology. 64(6):966–72. doi:10.1212/01.WNL.0000157282.76715.B1.
   PubMed Web of Science ®Google Scholar
• McLelland GL, Goiran T, Yi W, Dorval G, Chen CX, Lauinger ND, Krahn AI, Valimehr S, Rakovic A, Rouiller I, et al. Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. Elife. 2018;7:e32866.
   PubMed Web of Science ®Google Scholar
• Liao C, Ashley N, Diot A, Morten K, Phadwal K, Williams A, Fearnley I, Rosser L, Lowndes J, Fratter C, et al. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology. 2017;88(2):131–42. doi:10.1212/WNL.0000000000003491.
   PubMed Web of Science ®Google Scholar
• Zimmermann M, Reichert AS. 2017. How to get rid of mitochondria: crosstalk and regulation of multiple mitophagy pathways. Biol Chem. 399(1):29–45. doi:10.1515/hsz-2017-0206.
   PubMed Web of Science ®Google Scholar
• Xiao B, Goh JY, Xiao L, Xian H, Lim KL, Liou YC. Reactive oxygen species trigger Parkin/PINK1 pathway-dependent mitophagy by inducing mitochondrial recruitment of Parkin. J Biol Chem. 2017 Oct 6;292(40):16697–708. doi:10.1074/jbc.M117.787739.
   PubMed Web of Science ®Google Scholar
• Lee H, Yoon Y. 2018. Mitochondrial membrane dynamics-functional positioning of OPA1. Antioxidants (Basel). 7(12):186. doi:10.3390/antiox7120186.
   Google Scholar
• Millet AM, Bertholet AM, Daloyau M, Reynier P, Galinier A, Devin A, Wissinguer B, Belenguer P, Davezac N. 2016. Loss of functional OPA1 unbalances redox state: implications in dominant optic atrophy pathogenesis. Ann Clin Transl Neurol. 3(6):408–21. doi:10.1002/acn3.305.
   PubMed Web of Science ®Google Scholar
• Kushnareva Y, Seong Y, Andreyev AY, Kuwana T, Kiosses WB, Votruba M, Newmeyer DD. Mitochondrial dysfunction in an Opa1(Q285STOP) mouse model of dominant optic atrophy results from Opa1 haploinsufficiency. Cell Death Dis. 2016;7(7):e2309. doi:10.1038/cddis.2016.160.
   PubMed Web of Science ®Google Scholar
• Chun BY, Rizzo JF 3rd. 2016. Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. Curr Opin Ophthalmol. 27(6):475–80. doi:10.1097/ICU.0000000000000314.
   PubMed Web of Science ®Google Scholar
• Spiegel R, Saada A, Flannery PJ, Burte F, Soiferman D, Khayat M, Eisner V, Vladovski E, Taylor RW, Bindoff LA, et al. Fatal infantile mitochondrial encephalomyopathy, hypertrophic cardiomyopathy and optic atrophy associated with a homozygous OPA1 mutation. J Med Genet. 2016;53(2):127–31. doi:10.1136/jmedgenet-2015-103361.
   PubMed Web of Science ®Google Scholar
• Del Dotto V, Fogazza M, Musiani F, Maresca A, Aleo SJ, Caporali L, La Morgia C, Nolli C, Lodi T, Goffrini P, et al. Deciphering OPA1 mutations pathogenicity by combined analysis of human, mouse and yeast cell models. Biochim Biophys Acta Mol Basis Dis. 2018;1864(10):3496–514. doi:10.1016/j.bbadis.2018.08.004.
   PubMed Web of Science ®Google Scholar
• Zhang J, Liu X, Liang X, Lu Y, Zhu L, Fu R, Ji Y, Fan W, Chen J, Lin B, et al. A novel ADOA-associated OPA1 mutation alters the mitochondrial function, membrane potential, ROS production and apoptosis. Sci Rep. 2017;7(1):5704. Published 2017 Jul 18. doi:10.1038/s41598-017-05571-y.
   PubMed Web of Science ®Google Scholar
• Olichon A, Landes T, Arnauné-Pelloquin L, Emorine LJ, Mils V, Guichet A, Delettre C, Hamel C, Amati-Bonneau P, Bonneau D, et al. Effects of OPA1 mutations on mitochondrial morphology and apoptosis: relevance to ADOA pathogenesis. J Cell Physiol. 2007;211(2):423–30. doi:10.1002/jcp.20950.
   PubMed Web of Science ®Google Scholar
• Gegg ME, Cooper JM, Chau KY, Rojo M, Schapira AH, Taanman JW. 2010. Mitofusin 1 and mitofusin 2 are ubiquitinated in a PINK1/parkin-dependent manner upon induction of mitophagy. Hum Mol Genet. 19(24):4861–70. doi:10.1093/hmg/ddq419.
   PubMed Web of Science ®Google Scholar