Nuclear genes involved in mitochondrial diseases caused by instability of mitochondrial DNA

Joanna Rusecka, Magdalena Kaliszewska, Ewa Bartnik, Katarzyna Tońska, Joanna Rusecka, Magdalena Kaliszewska, Ewa Bartnik, Katarzyna Tońska

Abstract

Mitochondrial diseases are defined by a respiratory chain dysfunction and in most of the cases manifest as multisystem disorders with predominant expression in muscles and nerves and may be caused by mutations in mitochondrial (mtDNA) or nuclear (nDNA) genomes. Most of the proteins involved in respiratory chain function are nuclear encoded, although 13 subunits of respiratory chain complexes (together with 2 rRNAs and 22 tRNAs necessary for their translation) encoded by mtDNA are essential for cell function. nDNA encodes not only respiratory chain subunits but also all the proteins responsible for mtDNA maintenance, especially those involved in replication, as well as other proteins necessary for the transcription and copy number control of this multicopy genome. Mutations in these genes can cause secondary instability of the mitochondrial genome in the form of depletion (decreased number of mtDNA molecules in the cell), vast multiple deletions or accumulation of point mutations which in turn leads to mitochondrial diseases inherited in a Mendelian fashion. The list of genes involved in mitochondrial DNA maintenance is long, and still incomplete.

Keywords: Depletion; Mitochondrial DNA deletions; Mitochondrial DNA instability; Mitochondrial diseases; Nuclear genes.

Conflict of interest statement

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Conflict of interest

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mitochondrial DNA instability types with their molecular backgrounds and diseases they cause. AR – autosomal recessive, AD – autosomal dominant
Fig. 2
Fig. 2
The main symptoms of the diseases caused by mitochondrial DNA instability

References

    1. Ahmed N, Ronchi D, Comi GP. Genes and pathways involved in adult onset disorders featuring muscle mitochondrial DNA instability. Int J Mol Sci. 2015;16(8):18054–18076. doi: 10.3390/ijms160818054.
    1. Antonenkov VD, Isomursu A, Mennerich D, Vapola MH, Weiher H, Kietzmann T, Hiltunen JK. The human mitochondrial DNA depletion syndrome gene MPV17 encodes a non-selective channel that modulates membrane potential. J Biol Chem. 2015;290(22):13840–13861. doi: 10.1074/jbc.M114.608083.
    1. Arpa J, Cruz-Martínez A, Campos Y, Gutiérrez-Molina M, García-Rio F, Pérez-Conde C, Martín MA, Rubio JC, Del Hoyo P, Arpa-Fernández A, Arenas J. Prevalence and progression of mitochondrial diseases: a study of 50 patients. Muscle Nerve. 2003;28(6):690–695. doi: 10.1002/mus.10507.
    1. Behin A, Jardel C, Claeys KG, Fagart J, Louha M, Romero NB, Laforet P, Eymard B, Lombes A. Adult cases of mitochondrial DNA depletion due to TK2 defect: an expanding spectrum. Neurology. 2012;78:644–648. doi: 10.1212/WNL.0b013e318248df2b.
    1. Bronckaers A, Gago F, Balzarini J, Liekens S. The dual role of thymidine phosphorylase in cancer development and chemotherapy. Med Res Rev. 2009;29(6):903–953. doi: 10.1002/med.20159.
    1. Cámara Y, Carreño-Gago L, Martín MA, Melià MJ, Blázquez A, Delmiro A, Garrabou G, Morén C, Díaz-Manera J, Gallardo E, Bornstein B, López-Gallardo E, Hernández-Lain A, San Millán B, Cancho E, Rodríguez-Vico JS, Martí R, García-Arumí E. Severe TK2 enzyme activity deficiency in patients with mild forms of myopathy. Neurology. 2015;84(22):2286–2288. doi: 10.1212/WNL.0000000000001644.
    1. Campbell C, Kolesar J, Kaufman B. Mitochondrial transcription factor a regulates mitochondrial transcription initiation, DNA packaging, and genome copy numer. Biochim Biophys Acta. 2012;1819(9–10):921–929. doi: 10.1016/j.bbagrm.2012.03.002.
    1. Capps GJ, Samuels D, Chinnery P. A model of the nuclear control of mitochondrial DNA replication. J Theor Biol. 2003;221:565–583. doi: 10.1006/jtbi.2003.3207.
    1. Capt C, Passamonti M, Breton S. The human mitochondrial genome may code for more than 13 proteins. Mitochondrial DNA A DNA Mapp Seq Anal. 2016;27(5):3098–3101.
    1. Cerritelli S, et al. Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol Cell. 2003;11:807–815. doi: 10.1016/S1097-2765(03)00088-1.
    1. Chen H, Vermulst M, Wang YE, Chomyn A, Prolla TA, McCaffery JM, Chan DC. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141(2):280–289. doi: 10.1016/j.cell.2010.02.026.
    1. Cieskielski G, Rosado-Ruiz F, Kaguni L. Purification and comparative assay of human mitochondrial single-stranded DNA-binding protein. Methods Mol Biol. 2016;1351:211–222. doi: 10.1007/978-1-4939-3040-1_16.
    1. DeBalsi K, Hoff K, Copeland W. Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases. Ageing Res Rev. 2016;33:89–104. doi: 10.1016/j.arr.2016.04.006.
    1. Dinwiddie G, Gaskin D, Chan K, Norrington J, McCleary R. Residential segregation, geographic proximity and type of services used: evidence for racial/ethnic disparities in mental health. Soc Sci Med. 2013;80:67–75. doi: 10.1016/j.socscimed.2012.11.024.
    1. DiRe M, Sembongi H, He J, Reyes A, Yasukawa T, Martinsson P, Bailey LJ, Goffart S, Boyd-Kirkup JD, Wong TS, Fersht AR, Spelbrink JN, Holt IJ. The accessory subunit of mitochondrial DNA polymerase γ determines the DNA content of mitochondrial nucleoids in human cultured cells. Nucleic Acids Res. 2009;37(17):5701–5713. doi: 10.1093/nar/gkp614.
    1. Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, Rustin P, Gustafsson CM, Larsson NG. Mitochondrial transcription factor a regulates mtDNA copy number in mammals. Hum Mol Genet. 2004;13(9):935–944. doi: 10.1093/hmg/ddh109.
    1. Elachouri G, Vidoni S, Zanna C, Pattyn A, Boukhaddaoui H, Gaget K, Yu-Wai-Man P, Gasparre G, Sarzi E, Delettre C, Olichon A, Loiseau D, Reynier P, Chinnery PF, Rotig A, Carelli V, Hamel CP, Rugolo M, Lenaers G. OPA1 links human mitochondrial genome maintenance to mtDNA replication and distribution. Genome Res. 2011;21:12–20. doi: 10.1101/gr.108696.110.
    1. Fahrner JA, Liu R, Perry MS, Klein J, Chan DC. A novel de novo dominant negative mutation in DNM1L impairs mitochondrial fission and presents as childhood epileptic encephalopathy. Am J Med Genet A. 2016;170A:2002–2011. doi: 10.1002/ajmg.a.37721.
    1. Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM. Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA. Nat Genet. 2002;31:289–294. doi: 10.1038/ng909.
    1. Filadi R, Greotti E, Turacchio G, Luini A, Pozzan T, Pizzo P. Mitofusin 2 ablation increases endoplasmic reticulum-mitochondria coupling. Proc Natl Acad Sci U S A. 2015;112(17):2174–2181. doi: 10.1073/pnas.1504880112.
    1. Friedman JR, Lackner LL, West M, DiBenedetto JR, Nunnari J, Voeltz GK. ER tubules mark sites of mitochondrial division. Science. 2011;334(6054):358–362. doi: 10.1126/science.1207385.
    1. García-Gómez S, Reyes A, Martínez-Jiménez MI, Sandra Chocrón E, Mourón S, Terrados G, Powell C, Salido E, Méndez J, Holt IJ, Blanco L. PrimPol, an archaic Primae/polymerase operating in human cells. Mol Cell. 2013;52(4):541–553. doi: 10.1016/j.molcel.2013.09.025.
    1. Goffart S, Cooper HM, Tyynismaa H, Wanrooij S, Suomalainen A, Spelbrink JN. Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. Hum Mol Genet. 2009;18(2):328–340. doi: 10.1093/hmg/ddn359.
    1. Gorman GS, Schaefer AM, Ng Y, Gomez N, Blakely EL, Alston CL, Feeney C, Horvath R, Yu-Wai-Man P, Chinnery PF, Taylor RW, Turnbull DM, McFarland R. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol. 2015;77(5):753–759. doi: 10.1002/ana.24362.
    1. Holt IJ, Reyes A (2012) Human mitochondrial DNA replication. Cold Spring Harb Perspect Biol 4(12): a012971
    1. Holt I, Lorimer H, Jacobs H. Coupled leading- and lagging-strand synthesis of mammalian mitochondrial DNA. Cell. 2000;100(5):515–524. doi: 10.1016/S0092-8674(00)80688-1.
    1. Hudson G, Chinnery P (2006) Mitochondrial DNA polymerase-g and human disease. Hum Mol Genet. 15 Spec No 2:R244–52
    1. Hudson G, Amati-Bonneau P, Blakely EL, Stewart JD, He L, Schaefer AM, Griffiths PG, Ahlqvist K, Suomalainen A, Reynier P, McFarland R, Turnbull DM, Chinnery PF, Taylor RW. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain. 2007;131(2):329–337. doi: 10.1093/brain/awm272.
    1. Javaida S, Ishtiaqa M, Shaikhb M, Hameeda A, Choudharya MI. Thymidine esters as substrate analogue inhibitors of angiogenic enzyme thymidine phosphorylase in vitro. Bioorg Chem. 2016;70:44–56. doi: 10.1016/j.bioorg.2016.11.007.
    1. Johnson A, Johnson KA. Exonuclease proofreading by human mitochondrial DNA polymerase. J Biol Chem. 2001;276:38097–38107.
    1. Jullig M, Eriksson S. Mitochondrial and submitochondrial localization of human deoxyguanosine kinase. Eur J Biochem. 2000;267:5466–5472. doi: 10.1046/j.1432-1327.2000.01607.x.
    1. Kang D, Kim S, Hamasaki N. Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion. 2007;7(1–2):39–44. doi: 10.1016/j.mito.2006.11.017.
    1. Kaukonen J, Juselius JK, Tiranti V, Kyttälä A, Zeviani M, Comi GP, Keränen S, Peltonen L, Suomalainen A. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science. 2000;289(5480):782–785. doi: 10.1126/science.289.5480.782.
    1. Kawamata H, Tiranti V, Magrané J, Chinopoulos C, Manfredi G. adPEO mutations in ANT1 impair ADP–ATP translocation in muscle mitochondria. Hum Mol Genet. 2011;20(15):2964–2974. doi: 10.1093/hmg/ddr200.
    1. Korhonen JA, Gaspari M, Falkenberg M. TWINKLE has 5′ → 3′ DNA Helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. J Biol Chem. 2003;278:48627–48632. doi: 10.1074/jbc.M306981200.
    1. Krishnan KJ, Reeve AK, Samuels DC, Chinnery PF, Blackwood JK, Taylor RW, Wanrooij S, Spelbrink JN, Lightowlers RN, Turnbull DM. What causes mitochondrial DNA deletions in human cells? Nat Genet. 2008;40(3):275–279. doi: 10.1038/ng.f.94.
    1. Kühl I, Miranda M, Posse V, Milenkovic D, Mourier A, Siira SJ, Bonekamp NA, Neumann U, Filipovska A, Polosa PL, Gustafsson CM, Larsson NG. POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA. Sci Adv. 2016;2:8. doi: 10.1126/sciadv.1600963.
    1. Lamantea E, Tiranti V, Bordoni A, Toscano A, Bono F, Servidei S, Papadimitriou A, Spelbrink H, Silvestri L, Casari G, Comi GP, Zeviani M (2002) Mutations of mitochondrial DNA polymerase γA are a freuquent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann Neurol 52:211–219
    1. Lee YS, Kennedy WD, Yin YW. Structural insights into human mitochondrial DNA replication and disease-related polymerase mutations. Cell. 2009;139(2):312–324. doi: 10.1016/j.cell.2009.07.050.
    1. Lightowlers R, Taylor R, Turnbull D. Mutations causing mitochondrial disease: what is new and what challenges remain? Science. 2015;349:1494–1499. doi: 10.1126/science.aac7516.
    1. Linkowska K, Jawień A, Marszałek A, Malyarchuk BA, Tońska K, Bartnik E, Skonieczna K, Grzybowski T. Mitochondrial DNA polymerase γ mutations and their implications in mtDNA alterations in colorectal cancer. Ann Hum Genet. 2015;79:320–328. doi: 10.1111/ahg.12111.
    1. Litonin D, Sologub M, Shi Y, Savkina M, Anikin M, Falkenberg M, Gustafsson CM, Temiakov D. Human mitochondrial transcription revisited: only TFAM and TFB2M are required for transcription of the mitochondrial genes in vitro. J Biol Chem. 2010;285:18129–18133. doi: 10.1074/jbc.C110.128918.
    1. Liu Y, Wang X, Chen XJ. Misfolding of mutant adenine nucleotide translocase in yeast supports a novel mechanism of Ant1-induced muscle diseases. Mol Biol Cell. 2015;26(11):1985–1994. doi: 10.1091/mbc.E15-01-0030.
    1. Lodeiro M, Uchida A, Bestwick M, Moustafa I, Arnold J, Shadel G, Cameron C. Transcription from the second heavy-strand promoter of human mtDNA is repressed by transcription factor a in vitro. Proc Natl Acad Sci U S A. 2012;109(17):6513–6518. doi: 10.1073/pnas.1118710109.
    1. Losón OC, Song Z, Chen H, Chan DC. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell. 2013;24(5):659–667. doi: 10.1091/mbc.E12-10-0721.
    1. MacVicar T, Langer T. OPA1 processing in cell death and disease – the long and short of it. J Cell Sci. 2016;129(12):2297–2306. doi: 10.1242/jcs.159186.
    1. Maier D, Farr C, Poeck B, Alahari A, Vogel M, Fischer S, Kaguni LS, Schneuwly S. Mitochondrial single-stranded DNA-binding protein is required for mitochondrial DNA replication and development in Drosophila Melanogaster. Mol Biol Cell. 2001;12:821–830. doi: 10.1091/mbc.12.4.821.
    1. Manusco M, Filosto M, Bonilla E. Mitochondrial myopathy of childhood associated with mitochondrial DNA depletion and a homozygous mutation (T77M) in the TK2 gene. Arch Neurol. 2003;60(7):1007–1009. doi: 10.1001/archneur.60.7.1007.
    1. Martin-Garcia J (2013) Mitochondria and their role in cardiovascular disease. In: Introduction to mitochondria in the heart. Springer, Boston, pp 63–65
    1. McKinney E, Oliveira M. Replicating animal mitochondrial DNA. Genet Mol Biol. 2013;36(3):308–315. doi: 10.1590/S1415-47572013000300002.
    1. Milenkovic D, Matic S, Kühl I, Ruzzenente B, Freyer C, Jemt E, Park CB, Falkenberg M, Larsson NG. TWINKLE is an essential mitochondrial helicase required for synthesis of nascent D-loop strands and complete mtDNA replication. Hum Mol Genet. 2013;22(10):1983–1993. doi: 10.1093/hmg/ddt051.
    1. Minczuk M, He J, Duch AM, Ettema TJ, Chlebowski A, Dzionek K, Nijtmans L, Huynen MA, Holt IJ. TEFM (c17orf42) is necessary for transcription of human mtDNA. Nucleic Acids Res. 2011;39(10):4284–4299. doi: 10.1093/nar/gkq1224.
    1. Moustafa IM, Uchida A, Wang Y, Yennawar N, Cameron CE. Structural models of mammalian mitochondrial transcription factor B2. Biochim Biophys Acta. 2015;1849(8):987–1002. doi: 10.1016/j.bbagrm.2015.05.010.
    1. Naïmi M, Bannwarth S, Procaccio V, Pouget J, Desnuelle C, Pellissier JF, Rötig A, Munnich A, Calvas P, Richelme C, Jonveaux P, Castelnovo G, Simon M, Clanet M, Wallace D, Paquis-Flucklinger V. Molecular analysis of ANT1, TWINCLE and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. Eur J Hum Genet. 2006;14(8):917–922. doi: 10.1038/sj.ejhg.5201627.
    1. Nass MM, Nass S. Intramitochondrial fibers with DNA characteristics. I. Fixation and electron staining reactions. J Cell Biol. 1963;19:593–610. doi: 10.1083/jcb.19.3.593.
    1. Neckelmann N, Li K, Wade RP, Shuster R, Wallace DC. cDNA sequence of a human skeletal muscle ADP/ATP translocator: lack of a leader peptide, divergence from a fibroblast translocator cDNA, and coevolution with mitochondrial DNA genes. Proc Natl Acad Sci U S A. 1987;84(21):7580–7584. doi: 10.1073/pnas.84.21.7580.
    1. Nicholls TJ, Zsurka G, Peeva V, Schöler S, Szczesny RJ, Cysewski D, Reyes A, Kornblum C, Sciacco M, Moggio M, Dziembowski A, Kunz WS, Minczuk M. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease. Hum Mol Genet. 2014;23(23):6147–6162. doi: 10.1093/hmg/ddu336.
    1. Nikkanen J, Forsström S, Euro L, Paetau I, Kohnz RA, Wang L, Chilov D, Viinamäki J, Roivainen A, Marjamäki P, Liljenbäck H, Ahola S, Buzkova J, Terzioglu M, Khan NA, Pirnes-Karhu S, Paetau A, Lönnqvist T, Sajantila A, Isohanni P, Tyynismaa H, Nomura DK, Battersby BJ, Velagapudi V, Carroll CJ, Suomalainen A. Mitochondrial DNA replication defects disturb cellular dNTP pools and remodel one-carbon metabolism. Cell Metab. 2016;23:635–648. doi: 10.1016/j.cmet.2016.01.019.
    1. Oliveira M, Haukka J, Kaguni L (2015) Evolution of the Metazoan Mitochondrial Replicase. Genome Biol Evol 7(4):943–959
    1. Paradas C, Gutierrez Rios P, Rivas E, Carbonell P, Hirano M, DiMauro S. TK2 mutation presenting as indolent myopathy. Neurology. 2013;80:504–506. doi: 10.1212/WNL.0b013e31827f0ff7.
    1. Paramasivam A, Meena A, Pedaparthi L, Jyothi V, Uppin MS, Jabeen SA, Sundaram C, Thangaraj K. Novel mutation in TWNK associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging. Mitochondrion. 2016;26:81–85. doi: 10.1016/j.mito.2015.12.006.
    1. Pebay-Peyroula E, Dahout-Gonzalez C, Kahn R, Trézéguet V, Lauquin G, Brandolin G. Structure of mitochondrial ADP/ATP carrier in complex with carboxyatractyloside. Nature. 2003;426:39–44. doi: 10.1038/nature02056.
    1. Pfeffer G, Gorman GS, Griffin H, Kurzawa-Akanbi M, Blakely EL, Wilson I, Sitarz K, Moore D, Murphy JL, Alston CL, Pyle A, Coxhead J, Payne B, Gorrie GH, Longman C, Hadjivassiliou M, McConville J, Dick D, Imam I, Hilton D, Norwood F, Baker MR, Jaiser SR, Yu-Wai-Man P, Farrell M, McCarthy A, Lynch T, McFarland R, Schaefer AM, Turnbull DM, Horvath R, Taylor RW, Chinnery PF. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. Brain. 2014;137(Pt 5):1323–1336. doi: 10.1093/brain/awu060.
    1. Pfeffer G, Pyle A, Griffin H, Miller J, Wilson V, Turnbull L, Fawcett K, Sims D, Eglon G, Hadjivassiliou M, Horvath R, Németh A, Chinnery PF. SPG7 mutations are a common cause of undiagnosed ataxia. Neurology. 2015;84(11):1174–1176. doi: 10.1212/WNL.0000000000001369.
    1. Picca A, Lezza A. Regulation of mitochondrial biogenesis through TFAM–mitochondrial DNA interactions: useful insights from aging and calorie restriction studies. Mitochondrion. 2015;25:67–75. doi: 10.1016/j.mito.2015.10.001.
    1. Pontarin G, Ferraro P, Bee L, Reichard P, Bianchi V. Mammalian ribonucleotide reductase subunit p53R2 is required for mitochondrial DNA replication and DNA repair in quiescent cells. Proc Natl Acad Sci U S A. 2012;109(33):13302–13307. doi: 10.1073/pnas.1211289109.
    1. Posse V, Shahzad S, Falkenberg M, Hällberg M, Gustafsson CM. TEFM is a potent stimulator of mitochondrial transcription elongation in vitro. Nucleic Acids Res. 2015;43(5):2615–2624. doi: 10.1093/nar/gkv105.
    1. Reyes A, Melchionda L, Nasca A, Carrara F, Lamantea E, Zanolini A, Lamperti C, Fang M, Zhang J, Ronchi D, Bonato S, Fagiolari G, Moggio M, Ghezzi D, Zeviani M. RNASEH1 mutations impair mtDNA replication and cause adult-onset mitochondrial encephalomyopathy. Am J Hum Genet. 2015;97:186–193. doi: 10.1016/j.ajhg.2015.05.013.
    1. Ronchi D, Garone C, Bordoni A, Gutierrezrios P, Calvo SE, Ripolone M, Ranieri M, Rizzuti M, Villa L, Magri F, Corti S, Bresolin N, Mootha VK, Moggio M, DiMauro S, Comi GP, Sciacco M. Next-generation sequencing reveals DGUOK mutations in adult patients with mitochondrial DNA multiple deletions. Brain. 2012;135:3404–3415. doi: 10.1093/brain/aws258.
    1. Ronchi D, Di Fonzo A, Lin W, Bordoni A, Liu C, Fassone E, Pagliarani S, Rizzuti M, Zheng L, Filosto M, Ferrò MT, Ranieri M, Magri F, Peverelli L, Li H, Yuan YC, Corti S, Sciacco M, Moggio M, Bresolin N, Shen B, Comi GP. Mutations in DNA2 link progressive Myopathy to mitochondrial DNA instability. Am J Hum Genet. 2013;92(2):293–300. doi: 10.1016/j.ajhg.2012.12.014.
    1. Ruhanen H, Borriea S, Szabadkaibe G, Tyynismaaa H, Jones A, Kangc D, Taanmande JW, Yasukawa T. Mitochondrial single-stranded DNA binding protein is required for maintenance of mitochondrial DNA and 7S DNA but is not required for mitochondrial nucleoid organization. Biochim Biophys Acta (BBA) Mol Cell Res Vol. 2010;1803(8):931–939. doi: 10.1016/j.bbamcr.2010.04.008.
    1. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat Genet. 2001;29:342–344. doi: 10.1038/ng751.
    1. Sánchez-Ferrero E, Coto E, Beetz C, Gámez J, Corao AI, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual-Pascual SI, López de Munaín A, Garcia-Barcina MJ, Alvarez V. SPG7 mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V. Clin Genet. 2013;83:257–262. doi: 10.1111/j.1399-0004.2012.01896.x.
    1. Schatz G. The isolation of possible mitochondrial precursor structures from aerobically grown baker’s yeast. Biochem Biophys Res Commun. 1963;12:448–451. doi: 10.1016/0006-291X(63)90313-9.
    1. Scheibye-Knudsen M, Fang EF, Croteau DL, Wilson DM, Bohr VA. Protecting the mitochondrial powerhouse. Trends Cell Biol. 2015;25(3):158–170. doi: 10.1016/j.tcb.2014.11.002.
    1. Shokolenko I, Alexeyev M. Mitochondrial DNA: a disposable genome? Biochim Biophys Acta (BBA) Mol Basis Dis. 2015;1852:1805–1809. doi: 10.1016/j.bbadis.2015.05.016.
    1. Skladal D, Halliday J, Thorburn DR. Minimum birth prevalence of mitochondrial respiratory chain disorders in children. Brain. 2003;126:1905–1912. doi: 10.1093/brain/awg170.
    1. Spinazzola A, Viscomi C, Fernandez-Vizarra E, Carrara F, D'Adamo P, Calvo S, Marsano RM, Donnini C, Weiher H, Strisciuglio P, Parini R, Sarzi E, Chan A, DiMauro S, Rötig A, Gasparini P, Ferrero I, Mootha VK, Tiranti V, Zeviani M. MPV17 encodes an inner mitochondrial membrane protein and is mutated in infantile hepatic mitochondrial DNA depletion. Nat Genet. 2006;38:570–575. doi: 10.1038/ng1765.
    1. Stiles AR, Simon MT, Stover A, Eftekharian S, Khanlou N, Wang HL, Magaki S, Lee H, Partynski K, Dorrani N, Chang R, Martinez-Agosto JA, Abdenur JE. Mutations in TFAM, encoding mitochondrial transcription factor a, cause neonatal liver failure associated with mtDNA depletion. Mol Genet Metab. 2016;119:91–99. doi: 10.1016/j.ymgme.2016.07.001.
    1. Suomalainen A, Isohanni P. Mitochondrial DNA depletion syndromes – many genes, common mechanisms. Neuromuscul Disord. 2010;20:429–437. doi: 10.1016/j.nmd.2010.03.017.
    1. Szymanski MR, Kuznetsov VB, Shumate C, Meng Q, Lee YS, Patel G, Patel S, Yin YW. Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase. EMBO. 2015;34(14):1959–1970. doi: 10.15252/embj.201591520.
    1. Tyynismaa H, Sembongi H, Bokori-Brown M, Granycome C, Ashley N, Poulton J, Jalanko A, Spelbrink JN, Holt IJ, Suomalainen A. Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. Hum Mol Genet. 2004;13(24):3219–3227. doi: 10.1093/hmg/ddh342.
    1. Tyynismaa H, Peltola K, Wanrooij S, Lappalainen I. Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc Natl Acad Sci U S A. 2005;102(49):17687–17692. doi: 10.1073/pnas.0505551102.
    1. Tyynismaa H, Sun R, Ahola-Erkkilä S, Almusa H, Pöyhönen R, Korpela M, Honkaniemi J, Isohanni P, Paetau A, Suomalainen L (2012) Thymidine kinase 2 mutations in autosomal recessive progressive external ophthalmoplegia with multiple mitochondrial DNA deletions. Hum Mol Genet 21(1):66–75
    1. Uhler JP, Thörn C, Nicholls TJ, Matic S, Milenkovic D, Gustafsson CM, Falkenberg M. MGME1 processes flaps into ligatable nicks in concert with DNA polymerase γ during mtDNA replication. Nucleic Acids Res. 2016;44(12):5861–5871. doi: 10.1093/nar/gkw468.
    1. Van Dyck E, Foury F, Stillman B, Brill SJ. Single-stranded DNA binding protein required for mitochondrial DNA replication in S. cerevisiae is homologous to E. coli SSB. EMBO. 1992;11:3421–3430.
    1. Vielhaber S, Debska-Vielhaber G, Peeva V, Schoeler S, Kudin AP, Minin I, Schreiber S, Dengler R, Kollewe K, Zuschratter W, Kornblum C, Zsurka G, Kunz WS. Mitofusin 2 mutations affect mitochondrial function by mitochondrial DNA depletion. Acta Neuropathol. 2013;125(2):245–256. doi: 10.1007/s00401-012-1036-y.
    1. Wang L, Saada A, Eriksson S. Kinetic properties of mutant human thymidine kinase 2 suggest a mechanism for mitochondrial DNA depletion myopathy. J Biol Chem. 2003;278:6963–6968. doi: 10.1074/jbc.M206143200.
    1. Wong LJ. Next generation molecular diagnosis of mitochondrial disorders. Mitochondrion. 2013;13:379–387. doi: 10.1016/j.mito.2013.02.001.
    1. Wortmann SB, Koolen DA, Smeitink JA, van den Heuvel L, Rodenburg RJ. Whole exome sequencing of suspected mitochondrial patients in clinical practice. J Inherit Metab Dis. 2015;38(3):437–443. doi: 10.1007/s10545-015-9823-y.
    1. Yoon G, Malam Z, Paton T, Marshall CR, Hyatt E, Ivakine Z, Scherer SW, Lee KS, Hawkins C, Cohn RD. Lethal disorder of mitochondrial fission caused by mutations in DNM1L. J Pediatr. 2016;171:313–316. doi: 10.1016/j.jpeds.2015.12.060.
    1. Young M, Copeland W. Human mitochondrial DNA replication machinery and disease. Curr Opin Genet Dev. 2016;3:52–62. doi: 10.1016/j.gde.2016.03.005.
    1. Yu-Wai-Man P, Griffiths PG, Gorman GS, Lourenco CM, Wright AF, Auer-Grumbach M, Toscano A, Musumeci O, Valentino ML, Caporali L, Lamperti C, Tallaksen CM, Duffey P, Miller J, Whittaker RG, Baker MR, Jackson MJ, Clarke MP, Dhillon B, Czermin B, Stewart JD, Hudson G, Reynier P, Bonneau D, Marques W, Jr, Lenaers G, McFarland R, Taylor RW, Turnbull DM, Votruba M, Zeviani M, Carelli V, Bindoff LA, Horvath R, Amati-Bonneau P, Chinnery PF. Multi-system neurological disease is common in patients with OPA1 mutations. Brain. 2010;133(Pt 3):771–786. doi: 10.1093/brain/awq007.

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