Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Nuclear Genetic Control Of Mitochondrial Translation In Skeletal Muscle Revealed In Patients With Mitochondrial Myopathy.

F. Sasarman, G. Karpati, E. Shoubridge
Published 2002 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Oxidative phosphorylation deficiencies can be caused by mutations in either the nuclear genome or the mitochondrial genome (mtDNA); however, most pathogenic mutations reported in adults occur in mtDNA. Such mutations often impair mitochondrial translation, and are associated with a characteristic muscle pathology consisting of a mosaic pattern of normal fibres interspersed with fibres that show mitochondrial proliferation (ragged-red fibres) and little or no complex IV (COX) activity. We investigated two adult patients with a severe mitochondrial myopathy in whom all muscle fibres showed mitochondrial proliferation with barely detectable COX activity - a pattern never before reported. Biochemical studies of the respiratory chain in muscle showed decreased activities of complexes I and IV (5% of control) and complex II+III (41% of control). Immunoblot analysis of nuclear and mitochondrial subunits of complexes I, III and IV showed a greater than 90% decrease in the steady-state level of these subunits in mature muscle, but no change in nuclear-encoded subunits of complexes II and V. A generalized mitochondrial translation defect was identified in pulse-label experiments in myotubes, but not in myoblasts cultured from both patients. This defect moved with the nucleus in patient cybrid cells. Myoblasts from one patient transplanted into the muscle bed of SCID mice differentiated into mature human muscle fibres that displayed a defect similar to that seen in the patient muscle. These results suggest a defect in a developmentally regulated nuclear factor important for mitochondrial translation in skeletal muscle.
This paper references
10.1111/J.1432-1033.1995.0235I.X
Cytochrome-c oxidase in developing rat heart. Enzymic properties and amino-terminal sequences suggest identity of the fetal heart and the adult liver isoform.
H. Schägger (1995)
10.1128/MCB.18.4.1826
Functional Interactions between Yeast Mitochondrial Ribosomes and mRNA 5′ Untranslated Leaders
N. S. Green-Willms (1998)
10.1016/S0960-8966(01)00248-6
Hypertrophic cardiomyopathy and mtDNA depletion. Successful treatment with heart transplantation
F. Santorelli (2002)
10.1016/S0140-6736(94)92257-8
Lack of voltage-dependent anion channel in human mitochondrial myopathies
M. Huizing (1994)
10.1074/jbc.273.46.30482
A Novel Isoform of the Mitochondrial Outer Membrane Protein VDAC3 via Alternative Splicing of a 3-Base Exon
M. J. Sampson (1998)
10.1172/JCI117011
High efficiency of muscle regeneration after human myoblast clone transplantation in SCID mice.
J. Huard (1994)
Molecular histology of mitochondrial diseases Mitochondrial DNA in Human Pathology
E A Shoubridge (1993)
10.1067/MHJ.2000.103934
Mitochondrial defects in cardiomyopathy and neuromuscular disease.
D. Wallace (2000)
Molecular histology of mitochondrial diseases
E. A. Shoubridge (1993)
10.1016/0022-510X(73)90078-6
Late onset mitochondrial myopathy.
H. Shibasaki (1973)
10.1038/90116
Human cells are protected from mitochondrial dysfunction by complementation of DNA products in fused mitochondria
T. Ono (2001)
10.1083/JCB.103.4.1423
Expression of muscle-gene-specific isozymes of phosphorylase and creatine kinase in innervated cultured human muscle
A. Martinuzzi (1986)
10.1016/0012-1606(91)90473-G
Emergence of the mature myosin phenotype in the rat diaphragm muscle.
W. LaFramboise (1991)
10.1146/ANNUREV.BI.65.070196.003023
Crosstalk between nuclear and mitochondrial genomes.
R. O. Poyton (1996)
10.1093/HMG/10.20.2277
Nuclear genetic defects of oxidative phosphorylation.
E. Shoubridge (2001)
10.1126/SCIENCE.2814477
Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation.
M. P. King (1989)
10.1016/S0145-2126(99)00160-5
From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes.
N. Gattermann (2000)
10.1152/JAPPL.1991.71.4.1225
Cytochrome c protein synthesis rate in rat skeletal muscle.
F. Booth (1991)
10.1203/00006450-198902000-00023
Disproportionate Deficiency of Iron-Sulfur Clusters and Subunits of Complex I in Mitochondrial Encephalomyopathy
T. Ichiki (1989)
Distribution and threshold expression of the tRNA(Lys) mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF).
L. Boulet (1992)
10.1073/PNAS.94.17.9063
Human argininosuccinate lyase: a structural basis for intragenic complementation.
M. A. Turner (1997)
10.1016/0925-4439(92)90095-5
Steady-state transcript levels of cytochrome c oxidase genes during human myogenesis indicate subunit switching of subunit VIa and co-expression of subunit VIIa isoforms.
J. Taanman (1992)
10.1152/AJPCELL.1988.254.5.C605
Functional significance of myosin transitions in single fibers of developing soleus muscle.
P. Reiser (1988)
10.1006/BBRC.1999.1758
Long-term analysis of differentiation in human myoblasts repopulated with mitochondria harboring mtDNA mutations.
C. Sobreira (1999)
10.1074/JBC.275.15.11207
Very Rare Complementation between Mitochondria Carrying Different Mitochondrial DNA Mutations Points to Intrinsic Genetic Autonomy of the Organelles in Cultured Human Cells*
J. Enríquez (2000)
10.1016/s0021-9258(18)53930-2
Cloning and functional expression in yeast of two human isoforms of the outer mitochondrial membrane channel, the voltage-dependent anion channel.
E. Blachly-Dyson (1993)
10.1038/15513
Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene
L. C. Papadopoulou (1999)
Rpm2, the protein subunit of mitochondrial RNase P in Saccharomyces cerevisiae, also has a role in the translation of mitochondrially encoded subunits of cytochrome c oxidase.
V. Stribinskis (2001)
Functional interactions between yeast mitochondrial ribosomes and mRNA 5 0 untranslated leaders
N S Green-Willms (1998)
10.1006/BMME.1996.0078
Diagnosis of complex I deficiency in patients with lactic acidemia using skin fibroblast cultures.
S. Pitkänen (1996)
Cytochrome c turnover in rat skeletal muscles.
F. Booth (1977)
10.1016/S0076-6879(96)64042-7
Use of myoblast cultures to study mitochondrial myopathies.
E. Shoubridge (1996)
10.1038/ng0595-47
MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNALys and premature translation termination
José Antonio Enriquez (1995)
10.1016/0304-3940(88)90384-9
Asynchronous regulation of muscle specific isozymes of creatine kinase, glycogen phosphorylase, lactic dehydrogenase and phosphoglycerate mutase in innervated and non-innervated cultured human muscle
A. Martinuzzi (1988)
10.1038/348651A0
A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies
Y. Goto (1990)
10.1002/ar.1078
Comparative studies on the expression patterns of three troponin T genes during mouse development
Q. Wang (2001)
10.1203/00006450-199605000-00003
Deficiency of the Voltage-Dependent Anion Channel: A Novel Cause of Mitochondriopathy
M. Huizing (1996)
10.1016/0022-510X(91)90088-O
Multiple defects of the mitochondrial respiratory chain in a mitochondrial encephalopathy (MERRF): A clinical, biochemical and molecular study
L. Bindoff (1991)
10.1111/J.1432-1033.1993.TB18342.X
Expression of human cytochrome c oxidase subunits during fetal development.
G. Bonne (1993)
10.1016/S0925-4439(97)00061-6
Expression of mtDNA and nDNA encoded respiratory chain proteins in chemically and genetically-derived Rho0 human fibroblasts: a comparison of subunit proteins in normal fibroblasts treated with ethidium bromide and fibroblasts from a patient with mtDNA depletion syndrome.
M. Marusich (1997)
10.1002/BIES.950181208
Mitochondrial genetics and human disease
L. Grossman (1996)
10.1016/s0021-9258(18)46988-8
Inhibition of mitochondrial protein synthesis promotes increased stability of nuclear-encoded respiratory gene transcripts.
Z. Chrzanowska-Lightowlers (1994)
10.1016/S0140-6736(94)92258-6
No aspirin in red wine
P. Janssen (1994)
10.1006/BBRC.2000.2487
Characterization of the human porin isoform 1 (HVDAC1) gene by amplification on the whole human genome: A tool for porin deficiency analysis.
A. Messina (2000)
10.1038/3804
SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome
Z. Zhu (1998)
Genetics of mitochondrial translation
T. D. Fox (1996)
Functional interactions between yeast mitochondrial ribosomes and mRNA 50 untranslated leaders
N. S. Green-Willms (1998)
10.1006/EXCR.1999.4407
Expression of the E6 and E7 genes of human papillomavirus (HPV16) extends the life span of human myoblasts.
Hanns Lochmüller (1999)
10.1016/S0140-6736(89)92897-3
MITOCHONDRIAL DNA DELETION IN PEARSON'S MARROW/PANCREAS SYNDROME
A. Rotig (1989)
10.1042/BJ1780569
The turnover of cytochrome c in different skeletal-muscle fibre types of the rat.
R. Terjung (1979)
10.1006/BMMB.1994.1042
Studies on human porin. XII. Eight monoclonal mouse anti-"porin 31HL" antibodies discriminate type 1 and type 2 mammalian porin channels/VDACs in western blotting and enzyme-linked immunosorbent assays.
H. Winkelbach (1994)
10.1016/s0021-9258(18)67519-2
In vivo developmental modifications of the expression of genes encoding muscle-specific enzymes in rat.
F. Schweighoffer (1986)



This paper is referenced by
10.1002/ajmg.a.36065
A distinct mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) phenotype associates with YARS2 mutations
Rojeen Shahni (2013)
10.1101/574806
Metformin rescues muscle function in BAG3 myofibrillar myopathy models
A. A. Ruparelia (2019)
10.1136/jmg.2003.016048
Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNAIle homoplasmic mutation in the mitochondrial genome
A. Limongelli (2004)
10.1016/j.cub.2013.02.019
A Mitochondrial Ribosomal and RNA Decay Pathway Blocks Cell Proliferation
U. Richter (2013)
10.1002/ana.20282
Defective mitochondrial translation caused by a ribosomal protein (MRPS16) mutation
C. Miller (2004)
NEUROSCIENCE FOR NEUROLOGISTS Mitochondria
P. Chinnery (2003)
10.1016/j.ymgme.2014.06.004
Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene.
L. Burrage (2014)
Non-neutral sequence variation in human mitochondrial DNA: selection against deleterious mutations and haplogroup-related polymorphisms
J. Moilanen (2003)
10.1136/jmedgenet-2012-101375
Whole-exome sequencing identifies a mutation in the mitochondrial ribosome protein MRPL44 to underlie mitochondrial infantile cardiomyopathy
C. J. Carroll (2013)
10.1002/humu.22098
A novel mutation in YARS2 causes myopathy with lactic acidosis and sideroblastic anemia
F. Sasarman (2012)
10.1093/HUMUPD/DMI042
The transmission of OXPHOS disease and methods to prevent this.
L. Jacobs (2006)
10.1177/08830738050200080701
Unusual Clinical Presentations in Four Cases of Leigh Disease, Cytochrome C Oxidase Deficiency, and SURF1 Gene Mutations
S. Tay (2005)
10.1093/brain/awq320
Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency
J. Kemp (2011)
The transmission of OXPHOS disease and methods to prevent this
E. Mc (2005)
10.1080/15548627.2020.1833500
Metformin rescues muscle function in BAG3 myofibrillar myopathy models.
Avnika A Ruparelia (2020)
10.1016/j.bbadis.2012.03.007
Adaptation of respiratory chain biogenesis to cytochrome c oxidase deficiency caused by SURF1 gene mutations.
Nikola Kovářová (2012)
10.1534/GENETICS.104.037473
Mitochondrial Translation
S. Chiron (2005)
10.1016/j.biocel.2015.06.018
Exposure to arginine analog canavanine induces aberrant mitochondrial translation products, mitoribosome stalling, and instability of the mitochondrial proteome.
S. Konovalova (2015)
10.1097/01.EHX.0000455682.80650.e
Histological and immunohistochemical study on the effect of aflatoxin B1 on the left ventricular muscle of adult male rabbit with reference to the protective role of melatonin
Gehan M. Soliman (2014)
10.1007/128_2013_457
Pathogenic implications of human mitochondrial aminoacyl-tRNA synthetases.
Hagen Schwenzer (2014)
10.1095/biolreprod.107.060806
Neutral Mitochondrial Heteroplasmy Alters Physiological Function in Mice1
B. M. Acton (2007)
10.1074/jbc.M512578200
A Rostrocaudal Muscular Dystrophy Caused by a Defect in Choline Kinase Beta, the First Enzyme in Phosphatidylcholine Biosynthesis*
R. Sher (2006)
Semantic Scholar Logo Some data provided by SemanticScholar