Nuclear control of respiratory gene expression in mammalian cells

The mitochondrial respiratory apparatus is the product of both nuclear and mitochondrial genes. The protein coding capacity of mtDNA is restricted to the expression of 13 respiratory subunits and thus nuclear genes play a predominant role in the biosynthesis of the respiratory chain and in the expression of the mitochondrial genome. Transcriptional regulators that act on both nuclear and mitochondrial genes have been implicated in the bi‐genomic expression of the respiratory chain. Mitochondrial transcription is directed by a small number of nucleus‐encoded factors (Tfam, TFB1M, TFB2M, mTERF). The expression of these factors is coordinated with that of nuclear respiratory proteins through the action of transcriptional activators and coactivators. In particular, environmental signals induce the expression of PGC‐1 family coactivators (PGC‐1α, PGC‐1β, and PRC), which in turn target specific transcription factors (NRF‐1, NRF‐2, and ERRα) in the expression of respiratory genes. This system provides a mechanism for linking respiratory chain expression to environmental conditions and for integrating it with other functions related to cellular energetics. J. Cell. Biochem. 97: 673–683, 2006. © 2005 Wiley‐Liss, Inc.

[1]  G. Shadel,et al.  Mitochondrial DNA maintenance in vertebrates. , 1997, Annual review of biochemistry.

[2]  Bruce M. Spiegelman,et al.  Towards a molecular understanding of adaptive thermogenesis , 2000, Nature.

[3]  H. Hoppeler,et al.  Plasticity of skeletal muscle mitochondria: structure and function. , 2003, Medicine and science in sports and exercise.

[4]  G. Shadel,et al.  A Human Mitochondrial Transcription Factor Is Related to RNA Adenine Methyltransferases and Binds S-Adenosylmethionine , 2002, Molecular and Cellular Biology.

[5]  M. Noël,et al.  Initiation binding repressor, a factor that binds to the transcription initiation site of the histone h5 gene, is a glycosylated member of a family of cell growth regulators [corrected] , 1995, Molecular and cellular biology.

[6]  R. Scarpulla,et al.  Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. , 2004, Genes & development.

[7]  Daniel P. Kelly,et al.  Peroxisome Proliferator-activated Receptor Coactivator-1α (PGC-1α) Coactivates the Cardiac-enriched Nuclear Receptors Estrogen-related Receptor-α and -γ , 2002, The Journal of Biological Chemistry.

[8]  G. Shadel,et al.  Human Mitochondrial Transcription Factor B1 Interacts with the C-Terminal Activation Region of h-mtTFA and Stimulates Transcription Independently of Its RNA Methyltransferase Activity , 2003, Molecular and Cellular Biology.

[9]  K. Baar.  Involvement of PPARγ co-activator-1, nuclear respiratory factors 1 and 2, and PPARα in the adaptive response to endurance exercise , 2004 .

[10]  Daniel P. Kelly,et al.  PGC-1α Coactivates the Cardiac-enriched Nuclear Receptors ERRα and γ via Novel Leucine-rich Interaction Interfaces , 2002 .

[11]  I. Kola,et al.  The ETS Transcription Factor GABPα Is Essential for Early Embryogenesis , 2004, Molecular and Cellular Biology.

[12]  S. McKnight,et al.  Purification of a set of cellular polypeptides that bind to the purine-rich cis-regulatory element of herpes simplex virus immediate early genes. , 1989, Genes & development.

[13]  R. Scarpulla.  Molecular Biology of the OXPHOS System , 2004 .

[14]  V. Mootha,et al.  Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1 , 1999, Cell.

[15]  Christoph Handschin,et al.  Metabolic control through the PGC-1 family of transcription coactivators. , 2005, Cell metabolism.

[16]  D. Clayton.  Transcription and replication of mitochondrial DNA. , 2000, Human reproduction.

[17]  Y. Chinenov,et al.  The α and β Subunits of the GA-binding Protein Form a Stable Heterodimer in Solution , 2000, The Journal of Biological Chemistry.

[18]  D. Hardie,et al.  AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. , 2005, Cell metabolism.

[19]  Y. Matsushima,et al.  Drosophila Mitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells* , 2004, Journal of Biological Chemistry.

[20]  C. Weinberg,et al.  Urinary oestrogen patterns in long follicular phases. , 2000, Human reproduction.

[21]  R. Scarpulla,et al.  NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a new DNA-binding domain conserved in a family of developmental regulators. , 1993, Genes & development.

[22]  Jiandie D. Lin,et al.  PGC-1β in the Regulation of Hepatic Glucose and Energy Metabolism* , 2003, Journal of Biological Chemistry.

[23]  R. Scarpulla,et al.  Serine Phosphorylation within a Concise Amino-terminal Domain in Nuclear Respiratory Factor 1 Enhances DNA Binding* , 1997, The Journal of Biological Chemistry.

[24]  Y. Matsushima,et al.  Drosophila Mitochondrial Transcription Factor B1 Modulates Mitochondrial Translation but Not Transcription or DNA Copy Number in Schneider Cells* , 2005, Journal of Biological Chemistry.

[25]  Cynthia Wolberger,et al.  The Structure of GABPα/β: An ETS Domain- Ankyrin Repeat Heterodimer Bound to DNA , 1998 .

[26]  Kjell Hultenby,et al.  Mitochondrial transcription factor A regulates mtDNA copy number in mammals. , 2004, Human molecular genetics.

[27]  R. Scarpulla,et al.  Four structurally distinct, non-DNA-binding subunits of human nuclear respiratory factor 2 share a conserved transcriptional activation domain , 1995, Molecular and cellular biology.

[28]  Xiaohui S. Xie,et al.  Errα and Gabpa/b specify PGC-1α-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle , 2004 .

[29]  F. Martínez-Azorín.  The Mitochondrial Ribomotor Hypothesis , 2005, IUBMB life.

[30]  M. Martín,et al.  The alpha and beta subunits of the GA-binding protein form a stable heterodimer in solution. Revised model of heterotetrameric complex assembly. , 2000, Journal of Biological Chemistry.

[31]  D. Bogenhagen.  Interaction of mtTFB and mtRNA polymerase at core promoters for transcription of Xenopus laevis mtDNA. , 1996, The Journal of biological chemistry.

[32]  J. Taanman,et al.  The mitochondrial genome: structure, transcription, translation and replication. , 1999, Biochimica et biophysica acta.

[33]  P. Puigserver,et al.  Tissue-specific regulation of metabolic pathways through the transcriptional coactivator PGC1-α , 2005, International Journal of Obesity.

[34]  Jiandie D. Lin,et al.  Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice , 2004, Cell.

[35]  R. Scarpulla,et al.  Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. , 1993, Genes & development.

[36]  J. Saffitz,et al.  Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. , 2000, The Journal of clinical investigation.

[37]  J. Leszyk,et al.  Mitochondrial Biogenesis and Remodeling during Adipogenesis and in Response to the Insulin Sensitizer Rosiglitazone , 2003, Molecular and Cellular Biology.

[38]  R. Young,et al.  A common set of gene regulatory networks links metabolism and growth inhibition. , 2004, Molecular cell.

[39]  Denis Richard,et al.  Reduced Fat Mass in Mice Lacking Orphan Nuclear Receptor Estrogen-Related Receptor α , 2003, Molecular and Cellular Biology.

[40]  J. Huss,et al.  Nuclear receptor signaling and cardiac energetics. , 2004, Circulation research.

[41]  R. Scarpulla,et al.  Sequential Serum-dependent Activation of CREB and NRF-1 Leads to Enhanced Mitochondrial Respiration through the Induction of Cytochrome c * , 2000, The Journal of Biological Chemistry.

[42]  E. Oakeley,et al.  The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator 1alpha (PGC-1alpha)-induced mitochondrial biogenesis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[43]  C. Gustafsson,et al.  Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA , 2002, Nature Genetics.

[44]  G. Shadel,et al.  Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop , 2003, Nature Genetics.

[45]  R. Scarpulla,et al.  Mitochondrial DNA Instability and Peri-Implantation Lethality Associated with Targeted Disruption of Nuclear Respiratory Factor 1 in Mice , 2001, Molecular and Cellular Biology.

[46]  G. Barsh,et al.  Mitochondrial transcription factor A is necessary for mtDNA maintance and embryogenesis in mice , 1998, Nature Genetics.

[47]  Jiandie D. Lin,et al.  Bioenergetic Analysis of Peroxisome Proliferator-activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle Cells* , 2003, Journal of Biological Chemistry.

[48]  P. Reynier,et al.  PGC-1-related coactivator and targets are upregulated in thyroid oncocytoma. , 2003, Biochemical and biophysical research communications.

[49]  Jiandie D. Lin,et al.  Nutritional Regulation of Hepatic Heme Biosynthesis and Porphyria through PGC-1α , 2005, Cell.

[50]  R. Scarpulla,et al.  Nuclear activators and coactivators in mammalian mitochondrial biogenesis. , 2002, Biochimica et biophysica acta.

[51]  D. Ricquier,et al.  Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance , 2000, The Journal of physiology.

[52]  R. Scarpulla,et al.  Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators , 2005, Molecular and Cellular Biology.

[53]  R. Scarpulla,et al.  PGC-1-Related Coactivator, a Novel, Serum-Inducible Coactivator of Nuclear Respiratory Factor 1-Dependent Transcription in Mammalian Cells , 2001, Molecular and Cellular Biology.

[54]  C. Lelliott,et al.  Characterization of the human, mouse and rat PGC1 beta (peroxisome-proliferator-activated receptor-gamma co-activator 1 beta) gene in vitro and in vivo. , 2003, The Biochemical journal.