Preprint / Version 1

Therapeutic Options for MSTO1 Disorder


  • Sara Wang Astra Nova School



MSTO1 Disorder, mitochondrial diseases, metabolic diseases


One of the most prevalent types of metabolic diseases is mitochondrial diseases, which results from dysfunctional mitochondria. Mitochondrial diseases are estimated to affect 1 in 4,500 Americans. These diseases are caused by mutations in various genes, some of which are poorly understood. Mutations in one protein, MSTO1 (Misato 1), result in myopathy and ataxia in patients. MSTO1 is a mitochondrial protein that is involved in mitochondrial fusion and morphology. Mutations in this gene lead to impaired mitochondrial dynamics and mtDNA replication. Due to the rarity of this disorder and its ability to affect multiple parts of the body, there is no specific cure. In this review paper, I will outline the clinical manifestations associated with MSTO1 mutations and discuss possible therapeutic options for patients.


Avula S, Parikh S, Demarest S, Kurz J, Gropman A. Treatment of mitochondrial disorders. Curr Treat Options Neurol. 2014 Jun;16(6):292. doi: 10.1007/s11940-014-0292-7. PMID: 24700433; PMCID: PMC4067597.

Children’s Hospital of Philadelphia. Facts about mitochondria. 2018 September 11.,are%20made%20up%20of%20mitochondria.

Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases; Board on Health Sciences Policy; Institute of Medicine; National Academies of Sciences, Engineering, and Medicine; Claiborne A, English R, Kahn J, editors. Mitochondrial Replacement Techniques: Ethical, Social, and Policy Considerations. Washington (DC): National Academies Press (US); 2016 Mar 17. Summary. Available from: PMID: 27054230.

Donkervoort S, Sabouny R, Yun P, Gauquelin L, Chao KR, Hu Y, Al Khatib I, Töpf A, Mohassel P, Cummings BB, Kaur R, Saade D, Moore SA, Waddell LB, Farrar MA, Goodrich JK, Uapinyoying P, Chan SHS, Javed A, Leach ME, Karachunski P, Dalton J, Medne L, Harper A, Thompson C, Thiffault I, Specht S, Lamont RE, Saunders C, Racher H, Bernier FP, Mowat D, Witting N, Vissing J, Hanson R, Coffman KA, Hainlen M, Parboosingh JS, Carnevale A, Yoon G, Schnur RE; Care4Rare Canada Consortium; Boycott KM, Mah JK, Straub V, Foley AR, Innes AM, Bönnemann CG, Shutt TE. MSTO1 mutations cause mtDNA depletion, manifesting as muscular dystrophy with cerebellar involvement. Acta Neuropathol. 2019 Dec;138(6):1013-1031. doi: 10.1007/s00401-019-02059-z. Epub 2019 Aug 29. PMID: 31463572; PMCID: PMC6851037.

Gal A, Balicza P, Weaver D, Naghdi S, Joseph SK, Várnai P, Gyuris T, Horváth A, Nagy L, Seifert EL, Molnar MJ, Hajnóczky G. MSTO1 is a cytoplasmic pro-mitochondrial fusion protein, whose mutation induces myopathy and ataxia in humans. EMBO Mol Med. 2017 Jul;9(7):967-984. doi: 10.15252/emmm.201607058.

Glover EI, Martin J, Maher A, Thornhill RE, Moran GR, Tarnopolsky MA. A randomized trial of coenzyme Q10 in mitochondrial disorders. Muscle Nerve. 2010 Nov;42(5):739-48. doi: 10.1002/mus.21758. PMID: 20886510.

Hargreaves IP. Coenzyme Q10 as a therapy for mitochondrial disease. Int J Biochem Cell Biol. 2014 Apr;49:105-11. doi: 10.1016/j.biocel.2014.01.020. Epub 2014 Feb 2. PMID: 24495877.

Iwama K, Takaori T, Fukushima A, Tohyama J, Ishiyama A, Ohba C, Mitsuhashi S, Miyatake S, Takata A, Miyake N, Ito S, Saitsu H, Mizuguchi T, Matsumoto N. Novel recessive mutations in MSTO1 cause cerebellar atrophy with pigmentary retinopathy. J Hum Genet. 2018 Mar;63(3):263-270. doi: 10.1038/s10038-017-0405-8. Epub 2018 Jan 16. PMID: 29339779.

Kimura M, Okano Y. Human Misato regulates mitochondrial distribution and morphology. Exp Cell Res. 2007 Apr 15;313(7):1393-404. doi: 10.1016/j.yexcr.2007.02.004. Epub 2007 Feb 15. PMID: 17349998.

Koopman WJ, Beyrath J, Fung CW, Koene S, Rodenburg RJ, Willems PH, Smeitink JA. Mitochondrial disorders in children: toward development of small-molecule treatment strategies. EMBO Mol Med. 2016 Apr 1;8(4):311-27. doi: 10.15252/emmm.201506131. PMID: 26951622; PMCID: PMC4818752.

Li K, Jin R, Wu X. Whole-exome sequencing identifies rare compound heterozygous mutations in the MSTO1 gene associated with cerebellar ataxia and myopathy. Eur J Med Genet. 2020 Jan;63(1):103623. doi: 10.1016/j.ejmg.2019.01.013. Epub 2019 Jan 24. PMID: 30684668.

Mancuso M, Angelini C, Bertini E, Carelli V, Comi GP, Minetti C, Moggio M, Mongini T, Servidei S, Tonin P, Toscano A, Uziel G, Zeviani M, Siciliano G; Nation-wide Italian Collaborative Network of Mitochondrial Diseases. Fatigue and exercise intolerance in mitochondrial diseases. Literature revision and experience of the Italian Network of mitochondrial diseases. Neuromuscul Disord. 2012 Dec;22 Suppl 3(3-3):S226-9. doi: 10.1016/j.nmd.2012.10.012. PMID: 23182644; PMCID: PMC3526786.

Michio Hirano, Valentina Emmanuele, Catarina M. Quinzii; Emerging therapies for mitochondrial diseases. Essays Biochem 20 July 2018; 62 (3): 467–481. doi: 10.1042/EBC20170114.

Nasca A, Scotton C, Zaharieva I, Neri M, Selvatici R, Magnusson OT, Gal A, Weaver D, Rossi R, Armaroli A, Pane M, Phadke R, Sarkozy A, Muntoni F, Hughes I, Cecconi A, Hajnóczky G, Donati A, Mercuri E, Zeviani M, Ferlini A, Ghezzi D. Recessive mutations in MSTO1 cause mitochondrial dynamics impairment, leading to myopathy and ataxia. Hum Mutat. 2017 Aug;38(8):970-977. doi: 10.1002/humu.23262. Epub 2017 Jun 6. PMID: 28544275; PMCID: PMC5575512.

Nasca A, Di Meo I, Fellig Y, Saada A, Elpeleg O, Ghezzi D, Edvardson S. A novel homozygous MSTO1 mutation in Ashkenazi Jewish siblings with ataxia and myopathy. J Hum Genet. 2021 Aug;66(8):835-840. doi: 10.1038/s10038-020-00897-4. Epub 2021 Feb 22. PMID: 33612823.

Schultz-Rogers L, Ferrer A, Dsouza NR, Zimmermann MT, Smith BE, Klee EW, Dhamija R. Novel biallelic variants in MSTO1 associated with mitochondrial myopathy. Cold Spring Harb Mol Case Stud. 2019 Dec 13;5(6):a004309. doi: 10.1101/mcs.a004309. PMID: 31604776; PMCID: PMC6913144.

Rai PK, Craven L, Hoogewijs K, Russell OM, Lightowlers RN. Advances in methods for reducing mitochondrial DNA disease by replacing or manipulating the mitochondrial genome. Essays Biochem. 2018 Jul 20;62(3):455-465. doi: 10.1042/EBC20170113. PMID: 29950320; PMCID: PMC6056713.