核基因组的线粒体疾病
Mitochondrial disorders of the nuclear genome.
作者信息
Angelini C, Bello L, Spinazzi M, Ferrati C
机构信息
Department of Neurosciences, University of Padova, Italy.
出版信息
Acta Myol. 2009 Jul;28(1):16-23.
Abstract
BACKGROUND
Mitochondrial myopathies are regulated by two genomes: the nuclear DNA, and the mitochondrial DNA. While, so far, most studies have dealt with mitochondrial myopathies due to deletions or point mutations in the mitochondrial DNA, a new field of investigation is that of syndromes due to mutations in the nuclear DNA. These latter disorders have mendelian inheritance.
RESULTS
Three representative cases have been selected: one with COX deficiency and a Leigh syndrome due to a SURF1 gene mutation, one due to a defect of Coenzyme Q synthesis and one with dominant optic atrophy due to a mutation in the OPA1 gene.
CONCLUSIONS
Future developments will show that many neurodegenerative disorders are due to mutations of nuclear genes controlling mitochondrial function, fusion and fission.
摘要
背景
线粒体肌病由两个基因组调控：核DNA和线粒体DNA。迄今为止，大多数研究都集中在线粒体DNA缺失或点突变导致的线粒体肌病，而一个新的研究领域是核DNA突变引起的综合征。这些后者的疾病具有孟德尔遗传。
结果
选择了三个代表性病例：一个因SURF1基因突变导致细胞色素c氧化酶（COX）缺乏和 Leigh 综合征，一个因辅酶Q合成缺陷，一个因OPA1基因突变导致显性视神经萎缩。
结论
未来的发展将表明，许多神经退行性疾病是由于控制线粒体功能、融合和裂变的核基因突变所致。
相似文献
1
Mitochondrial disorders of the nuclear genome.核基因组的线粒体疾病
Acta Myol. 2009 Jul;28(1):16-23.
2
Ophthalmological manifestations in patients with Leigh syndrome.Leigh综合征患者的眼科表现。
Br J Ophthalmol. 2015 Apr;99(4):528-35. doi: 10.1136/bjophthalmol-2014-305704. Epub 2014 Oct 28.
3
Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders.线粒体遗传性疾病中的视网膜神经节细胞神经变性
Biochim Biophys Acta. 2009 May;1787(5):518-28. doi: 10.1016/j.bbabio.2009.02.024. Epub 2009 Mar 5.
4
Acute and late-onset optic atrophy due to a novel OPA1 mutation leading to a mitochondrial coupling defect.一种导致线粒体偶联缺陷的新型OPA1突变引起的急性和迟发性视神经萎缩。
Mol Vis. 2009;15:598-608. Epub 2009 Mar 27.
5
Cytochrome C oxydase deficiency: SURF1 gene investigation in patients with Leigh syndrome.细胞色素C氧化酶缺乏症：对Leigh综合征患者的SURF1基因研究
Biochem Biophys Res Commun. 2018 Mar 18;497(4):1043-1048. doi: 10.1016/j.bbrc.2018.02.169. Epub 2018 Feb 23.
6
Mutations in DNM1L, as in OPA1, result in dominant optic atrophy despite opposite effects on mitochondrial fusion and fission.DNM1L 中的突变，与 OPA1 中的突变一样，尽管对线粒体融合和裂变有相反的影响，但仍导致显性视神经萎缩。
Brain. 2017 Oct 1;140(10):2586-2596. doi: 10.1093/brain/awx219.
7
The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy 'plus' phenotype.MFN2 基因负责线粒体 DNA 不稳定和视神经萎缩“加号”表型。
Brain. 2012 Jan;135(Pt 1):23-34. doi: 10.1093/brain/awr323. Epub 2011 Dec 20.
8
Mitochondrial disorder with OPA1 mutation lacking optic atrophy.伴有OPA1突变但无视神经萎缩的线粒体疾病。
Mitochondrion. 2009 Jul;9(4):279-81. doi: 10.1016/j.mito.2009.03.001. Epub 2009 Mar 20.
9
Clinical and magnetic resonance imaging findings in patients with Leigh syndrome and SURF1 mutations.患有Leigh综合征和SURF1突变患者的临床及磁共振成像表现
Brain Dev. 2014 Oct;36(9):807-12. doi: 10.1016/j.braindev.2013.10.012. Epub 2013 Nov 18.
10
[Mitochondrial diseases in children including Leigh syndrome--biochemical and molecular background].[儿童线粒体疾病，包括 Leigh 综合征——生化与分子背景]
Postepy Biochem. 2008;54(2):161-8.
引用本文的文献
1
Clinical and Molecular Characterizations of Mitochondrial Disorders: A Tertiary-Care Center Experience.线粒体疾病的临床与分子特征：一家三级医疗中心的经验
Children (Basel). 2025 Aug 21;12(8):1102. doi: 10.3390/children12081102.
2
Peripheral Mitochondrial Dysfunction: A Potential Contributor to the Development of Metabolic Disorders and Alzheimer's Disease.外周线粒体功能障碍：代谢紊乱和阿尔茨海默病发展的潜在因素。
Biology (Basel). 2023 Jul 19;12(7):1019. doi: 10.3390/biology12071019.
3
Mitochondrial Dynamics during Development.发育过程中的线粒体动力学
Newborn (Clarksville). 2023 Jan-Mar;2(1):19-44. doi: 10.5005/jp-journals-11002-0053. Epub 2023 Apr 6.
4
Genetic perturbation of mitochondrial function reveals functional role for specific mitonuclear genes, metabolites, and pathways that regulate lifespan.遗传干扰线粒体功能揭示了特定的线粒体核基因、代谢物和调节寿命的途径的功能作用。
Geroscience. 2023 Aug;45(4):2161-2178. doi: 10.1007/s11357-023-00796-4. Epub 2023 Apr 22.
5
Pathogenic mtDNA variants, in particular single large-scale mtDNA deletions, are strongly associated with post-lingual onset sensorineural hearing loss in primary mitochondrial disease.致病性 mtDNA 变异体，特别是单个大片段 mtDNA 缺失，与原发性线粒体疾病的后天获得性感觉神经性听力损失密切相关。
Mol Genet Metab. 2022 Nov;137(3):230-238. doi: 10.1016/j.ymgme.2022.09.002. Epub 2022 Sep 19.
6
Transcriptional Analysis of Nuclear-Encoded Mitochondrial Genes in Eight Neurodegenerative Disorders: The Analysis of Seven Diseases in Reference to Friedreich's Ataxia.八种神经退行性疾病中核编码线粒体基因的转录分析：参照弗里德赖希共济失调对七种疾病的分析
Front Genet. 2021 Dec 20;12:749792. doi: 10.3389/fgene.2021.749792. eCollection 2021.
7
Beyond base excision repair: an evolving picture of mitochondrial DNA repair.超越碱基切除修复：线粒体 DNA 修复的不断发展的图景。
Biosci Rep. 2021 Oct 29;41(10). doi: 10.1042/BSR20211320.
8
Failure to Guard: Mitochondrial Protein Quality Control in Cancer.未能防护：癌症中的线粒体蛋白质质量控制。
Int J Mol Sci. 2021 Aug 2;22(15):8306. doi: 10.3390/ijms22158306.
9
Feature of Heart Rate Variability and Metabolic Mechanism in Female College Students with Depression.女性大学生抑郁症的心率变异性特征及代谢机制。
Biomed Res Int. 2020 Feb 27;2020:5246350. doi: 10.1155/2020/5246350. eCollection 2020.
10
Mutation of the Gene as the Cause of a Severe Hyperkinetic Movement Disorder.该基因的突变作为一种严重运动亢进性运动障碍的病因。
Mov Disord Clin Pract. 2019 Nov 7;7(1):88-90. doi: 10.1002/mdc3.12855. eCollection 2020 Jan.
本文引用的文献
1
A novel deletion in the GTPase domain of OPA1 causes defects in mitochondrial morphology and distribution, but not in function.OPA1鸟苷三磷酸酶结构域中的一种新型缺失会导致线粒体形态和分布出现缺陷，但不会影响其功能。
Hum Mol Genet. 2008 Nov 1;17(21):3291-302. doi: 10.1093/hmg/ddn225. Epub 2008 Aug 4.
2
Mitochondrial dysfunction as a cause of ageing.线粒体功能障碍是衰老的一个原因。
J Intern Med. 2008 Feb;263(2):167-78. doi: 10.1111/j.1365-2796.2007.01905.x.
3
A lethal defect of mitochondrial and peroxisomal fission.线粒体和过氧化物酶体分裂的致死性缺陷。
N Engl J Med. 2007 Apr 26;356(17):1736-41. doi: 10.1056/NEJMoa064436.
4
Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.孤立性线粒体脑病中与BCS1L基因突变相关的复合体III组装受损。
Hum Mol Genet. 2007 May 15;16(10):1241-52. doi: 10.1093/hmg/ddm072. Epub 2007 Apr 2.
5
Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases.神经退行性疾病中的氧化应激与线粒体功能障碍
Neuroscience. 2007 Apr 14;145(4):1233-48. doi: 10.1016/j.neuroscience.2006.10.056. Epub 2007 Feb 14.
6
Leigh syndrome with nephropathy and CoQ10 deficiency due to decaprenyl diphosphate synthase subunit 2 (PDSS2) mutations.因十聚异戊二烯二磷酸合酶亚基2（PDSS2）突变导致的伴有肾病和辅酶Q10缺乏的 Leigh 综合征。
Am J Hum Genet. 2006 Dec;79(6):1125-9. doi: 10.1086/510023. Epub 2006 Oct 27.
7
Thymidine phosphorylase gene mutations cause mitochondrial neurogastrointestinal encephalomyopathy (MNGIE).胸苷磷酸化酶基因突变导致线粒体神经胃肠性脑肌病（MNGIE）。
Intern Med. 2006;45(19):1103. doi: 10.2169/internalmedicine.45.6064. Epub 2006 Nov 1.
8
Mitochondrial dysfunction, oxidative stress and neurodegeneration.线粒体功能障碍、氧化应激与神经退行性变。
J Alzheimers Dis. 2006 Sep;10(1):59-73. doi: 10.3233/jad-2006-10110.
9
Clinical spectrum of mitochondrial DNA depletion due to mutations in the thymidine kinase 2 gene.胸苷激酶2基因突变导致的线粒体DNA耗竭的临床谱。
Arch Neurol. 2006 Aug;63(8):1122-6. doi: 10.1001/archneur.63.8.1122.
10
Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene.与线粒体聚合酶γ基因突变相关的表型谱
Brain. 2006 Jul;129(Pt 7):1674-84. doi: 10.1093/brain/awl088. Epub 2006 Apr 18.
Zotero 插件