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Nuclear transcription factors in mammalian mitochondria.

Leigh-Brown S, Enriquez JA, Odom DT - Genome Biol. (2010)

Bottom Line: Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression.Emerging genomics techniques may overcome outstanding challenges in this field.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.

ABSTRACT
Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression. Emerging genomics techniques may overcome outstanding challenges in this field.

Show MeSH
Organization of the mammalian mitochondrial genome. Thirteen protein-coding genes (yellow), twenty-two tRNA genes (red) and two rRNA genes (orange) are encoded on a single circular nucleic acid and transcribed from three promoters (blue): LSP, HSP1 and HSP2, which are situated in a single region called the D-loop, which contains regulatory sequences that control transcription from all three promoters, including motifs for DNA-binding proteins such as Tfam. The inner circle of genes is encoded on the (-) strand and transcribed from the LSP promoter. The outer circle of genes is encoded on the (+) strand and transcribed from the HSP1 and HSP2 promoters. Transcription from HSP2 is terminated distal to the 16S rRNA gene. The resulting three polycistronic transcripts are processed by enzymatic excision of the tRNAs (red). ATP6, ATP8, subunits of ATP synthase F0; Cox1, Cox2, Cox3, subunits of cytochrome oxidase; CytB, cytochrome B, Nd1, Nd2, Nd3, Nd4, Nd4L, Nd5, Nd6, subunits of NADH dehydrogenase.
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Figure 1: Organization of the mammalian mitochondrial genome. Thirteen protein-coding genes (yellow), twenty-two tRNA genes (red) and two rRNA genes (orange) are encoded on a single circular nucleic acid and transcribed from three promoters (blue): LSP, HSP1 and HSP2, which are situated in a single region called the D-loop, which contains regulatory sequences that control transcription from all three promoters, including motifs for DNA-binding proteins such as Tfam. The inner circle of genes is encoded on the (-) strand and transcribed from the LSP promoter. The outer circle of genes is encoded on the (+) strand and transcribed from the HSP1 and HSP2 promoters. Transcription from HSP2 is terminated distal to the 16S rRNA gene. The resulting three polycistronic transcripts are processed by enzymatic excision of the tRNAs (red). ATP6, ATP8, subunits of ATP synthase F0; Cox1, Cox2, Cox3, subunits of cytochrome oxidase; CytB, cytochrome B, Nd1, Nd2, Nd3, Nd4, Nd4L, Nd5, Nd6, subunits of NADH dehydrogenase.

Mentions: Mammalian cells store genetic information in two cellular compartments: the nucleus and the mitochondria. Mitochondrial DNA is packaged, handled and inherited independently of the nuclear genome, and far less is known about the regulation of mitochondrial gene expression compared with that of nuclear genes. As the singular site of the generation of adenosine triphosphate (ATP) by oxidative phosphorylation in the eukaryotic cell, the regulation of mitochondrial functions are complex and must be tightly regulated to respond to cellular metabolic requirements [1,2]. The majority of proteins present in mitochondria are encoded and transcribed in the nucleus [3], but the mitochondrial genome encodes a handful of proteins crucial for the generation of ATP (Figure 1). These proteins are transcribed and translated in the mitochondrial matrix and do not enter the cytoplasm [4,5]. Because both the nuclear and the mitochondrial genomes contribute to the mitochondrial proteome, their regulatory coordination is critical to cell survival and energy homeostasis [6]. This coordination is complicated by the distinct packaging and environment of the two genomes (Box 1).


Nuclear transcription factors in mammalian mitochondria.

Leigh-Brown S, Enriquez JA, Odom DT - Genome Biol. (2010)

Organization of the mammalian mitochondrial genome. Thirteen protein-coding genes (yellow), twenty-two tRNA genes (red) and two rRNA genes (orange) are encoded on a single circular nucleic acid and transcribed from three promoters (blue): LSP, HSP1 and HSP2, which are situated in a single region called the D-loop, which contains regulatory sequences that control transcription from all three promoters, including motifs for DNA-binding proteins such as Tfam. The inner circle of genes is encoded on the (-) strand and transcribed from the LSP promoter. The outer circle of genes is encoded on the (+) strand and transcribed from the HSP1 and HSP2 promoters. Transcription from HSP2 is terminated distal to the 16S rRNA gene. The resulting three polycistronic transcripts are processed by enzymatic excision of the tRNAs (red). ATP6, ATP8, subunits of ATP synthase F0; Cox1, Cox2, Cox3, subunits of cytochrome oxidase; CytB, cytochrome B, Nd1, Nd2, Nd3, Nd4, Nd4L, Nd5, Nd6, subunits of NADH dehydrogenase.
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Related In: Results  -  Collection

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Figure 1: Organization of the mammalian mitochondrial genome. Thirteen protein-coding genes (yellow), twenty-two tRNA genes (red) and two rRNA genes (orange) are encoded on a single circular nucleic acid and transcribed from three promoters (blue): LSP, HSP1 and HSP2, which are situated in a single region called the D-loop, which contains regulatory sequences that control transcription from all three promoters, including motifs for DNA-binding proteins such as Tfam. The inner circle of genes is encoded on the (-) strand and transcribed from the LSP promoter. The outer circle of genes is encoded on the (+) strand and transcribed from the HSP1 and HSP2 promoters. Transcription from HSP2 is terminated distal to the 16S rRNA gene. The resulting three polycistronic transcripts are processed by enzymatic excision of the tRNAs (red). ATP6, ATP8, subunits of ATP synthase F0; Cox1, Cox2, Cox3, subunits of cytochrome oxidase; CytB, cytochrome B, Nd1, Nd2, Nd3, Nd4, Nd4L, Nd5, Nd6, subunits of NADH dehydrogenase.
Mentions: Mammalian cells store genetic information in two cellular compartments: the nucleus and the mitochondria. Mitochondrial DNA is packaged, handled and inherited independently of the nuclear genome, and far less is known about the regulation of mitochondrial gene expression compared with that of nuclear genes. As the singular site of the generation of adenosine triphosphate (ATP) by oxidative phosphorylation in the eukaryotic cell, the regulation of mitochondrial functions are complex and must be tightly regulated to respond to cellular metabolic requirements [1,2]. The majority of proteins present in mitochondria are encoded and transcribed in the nucleus [3], but the mitochondrial genome encodes a handful of proteins crucial for the generation of ATP (Figure 1). These proteins are transcribed and translated in the mitochondrial matrix and do not enter the cytoplasm [4,5]. Because both the nuclear and the mitochondrial genomes contribute to the mitochondrial proteome, their regulatory coordination is critical to cell survival and energy homeostasis [6]. This coordination is complicated by the distinct packaging and environment of the two genomes (Box 1).

Bottom Line: Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression.Emerging genomics techniques may overcome outstanding challenges in this field.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, UK.

ABSTRACT
Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression. Emerging genomics techniques may overcome outstanding challenges in this field.

Show MeSH