The mitochondrial tRNALeu(UUR) mutation in MELAS: a model for pathogenesis

Eric A. Schon; Yasutoshi Koga; Mercy Davidson; Carlos T. Moraes; Michael P. King

doi:10.1016/0005-2728(92)90226-R

The mitochondrial tRNA^Leu(UUR) mutation in MELAS: a model for pathogenesis

Eric A. Schon, Yasutoshi Koga, Mercy Davidson, Carlos T. Moraes, Michael P. King

Research output: Contribution to journal › Article › peer-review

71 Scopus citations

Abstract

The A → G transition at nucleotide 3243 of the mitochondrial tRNA^Leu(UUR) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (ρ^o cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNA^Leu(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

Original language	English (US)
Pages (from-to)	206-209
Number of pages	4
Journal	Biochimica et Biophysica Acta - Bioenergetics
Volume	1101
Issue number	2
DOIs	https://doi.org/10.1016/0005-2728(92)90226-R
State	Published - 1992
Externally published	Yes

Keywords

Mitochondrial disease
Mitochondrion
mtDNA
Ribosome
rRNA
Translation

ASJC Scopus subject areas

Biophysics

Access to Document

10.1016/0005-2728(92)90226-R

Cite this

@article{d3d609e5916941bea5e6fc3e90bf3c61,

title = "The mitochondrial tRNALeu(UUR) mutation in MELAS: a model for pathogenesis",

abstract = "The A → G transition at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (ρo cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNALeu(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.",

keywords = "Mitochondrial disease, Mitochondrion, mtDNA, Ribosome, rRNA, Translation",

author = "Schon, {Eric A.} and Yasutoshi Koga and Mercy Davidson and Moraes, {Carlos T.} and King, {Michael P.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (NS28828 and AG08702), the Muscular Dystrophy Association, the Aaron Diamond Foundation, and by a grant from Libero and Graziella Danesi (Milano, Italy). M.P.K. is a recipient of the Harry Zimmerman Neuromuscular Disease Research Fellowship of the Muscular Dystrophy Association. Y.K. is the David Warfield Fellow in Ophthalmology of the New York Community Trust and the New York Academy of Medicine.",

year = "1992",

doi = "10.1016/0005-2728(92)90226-R",

language = "English (US)",

volume = "1101",

pages = "206--209",

journal = "Biochimica et Biophysica Acta - Bioenergetics",

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T1 - The mitochondrial tRNALeu(UUR) mutation in MELAS

T2 - a model for pathogenesis

AU - Schon, Eric A.

AU - Koga, Yasutoshi

AU - Davidson, Mercy

AU - Moraes, Carlos T.

AU - King, Michael P.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (NS28828 and AG08702), the Muscular Dystrophy Association, the Aaron Diamond Foundation, and by a grant from Libero and Graziella Danesi (Milano, Italy). M.P.K. is a recipient of the Harry Zimmerman Neuromuscular Disease Research Fellowship of the Muscular Dystrophy Association. Y.K. is the David Warfield Fellow in Ophthalmology of the New York Community Trust and the New York Academy of Medicine.

PY - 1992

Y1 - 1992

N2 - The A → G transition at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (ρo cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNALeu(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

AB - The A → G transition at nucleotide 3243 of the mitochondrial tRNALeu(UUR) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (ρo cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNALeu(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

KW - Mitochondrial disease

KW - Mitochondrion

KW - mtDNA

KW - Ribosome

KW - rRNA

KW - Translation

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