TY - JOUR
T1 - Mitochondrial transcription
T2 - Lessons from mouse models
AU - Peralta, Susana
AU - Wang, Xiao
AU - Moraes, Carlos T.
N1 - Funding Information:
This work was supported by NIH grants CA085700, AG036871, NS041777 and EY010804 . It was also supported by the Muscular Dystrophy Association and the James & Esther King Biomedical Research Program .
PY - 2012/9
Y1 - 2012/9
N2 - Mammalian mitochondrial DNA (mtDNA) is a circular double-stranded DNA genome of ~. 16.5 kilobase pairs (kb) that encodes 13 catalytic proteins of the ATP-producing oxidative phosphorylation system (OXPHOS), and the rRNAs and tRNAs required for the translation of the mtDNA transcripts. All the components needed for transcription and replication of the mtDNA are, therefore, encoded in the nuclear genome, as are the remaining components of the OXPHOS system and the mitochondrial translation machinery. Regulation of mtDNA gene expression is very important for modulating the OXPHOS capacity in response to metabolic requirements and in pathological processes. The combination of in vitro and in vivo studies has allowed the identification of the core machinery required for basal mtDNA transcription in mammals and a few proteins that regulate mtDNA transcription. Specifically, the generation of knockout mouse strains in the last several years, has been key to understanding the basis of mtDNA transcription in vivo. However, it is well accepted that many components of the transcription machinery are still unknown and little is known about mtDNA gene expression regulation under different metabolic requirements or disease processes. In this review we will focus on how the creation of knockout mouse models and the study of their phenotypes have contributed to the understanding of mitochondrial transcription in mammals. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
AB - Mammalian mitochondrial DNA (mtDNA) is a circular double-stranded DNA genome of ~. 16.5 kilobase pairs (kb) that encodes 13 catalytic proteins of the ATP-producing oxidative phosphorylation system (OXPHOS), and the rRNAs and tRNAs required for the translation of the mtDNA transcripts. All the components needed for transcription and replication of the mtDNA are, therefore, encoded in the nuclear genome, as are the remaining components of the OXPHOS system and the mitochondrial translation machinery. Regulation of mtDNA gene expression is very important for modulating the OXPHOS capacity in response to metabolic requirements and in pathological processes. The combination of in vitro and in vivo studies has allowed the identification of the core machinery required for basal mtDNA transcription in mammals and a few proteins that regulate mtDNA transcription. Specifically, the generation of knockout mouse strains in the last several years, has been key to understanding the basis of mtDNA transcription in vivo. However, it is well accepted that many components of the transcription machinery are still unknown and little is known about mtDNA gene expression regulation under different metabolic requirements or disease processes. In this review we will focus on how the creation of knockout mouse models and the study of their phenotypes have contributed to the understanding of mitochondrial transcription in mammals. This article is part of a Special Issue entitled: Mitochondrial Gene Expression.
KW - MTERF
KW - Mitochondria
KW - MtDNA
KW - TFAM
KW - Transcription
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U2 - 10.1016/j.bbagrm.2011.11.001
DO - 10.1016/j.bbagrm.2011.11.001
M3 - Review article
C2 - 22120174
AN - SCOPUS:84864321921
SN - 1874-9399
VL - 1819
SP - 961
EP - 969
JO - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
JF - Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
IS - 9-10
ER -