Differentiation of THP-1 monocytes to macrophages increased mitochondrial DNA copy number but did not increase expression of mitochondrial respiratory proteins or mitochondrial transcription factor A

Human mitochondrial transcription factor A is a 25-kDa protein that binds immediately upstream of the two major mitochondrial promoters, thereby leading to correct and efficient initiation of transcription. Although the nature of yeast mitochondrial promoters is significantly different from that of human promoters, a potential functional homolog of the human transcriptional activator protein has been previously identified in yeast mitochondria. The importance of the yeast protein in yeast mitochondrial DNA function has been shown by inactivation of its nuclear gene (ABF2) in Saccharomyces cerevisiae cells resulting in loss of mitochondrial DNA. We report here that the nuclear gene for human mitochondrial transcription factor A can be stably expressed in yeast cells devoid of the yeast homolog protein. The human protein is imported efficiently into yeast mitochondria, is processed correctly, and rescues the loss-of-mitochondrial DNA phenotype in a yeast abf2 strain, thus functionally substituting for the yeast protein. Both human and yeast proteins affect yeast mitochondrial transcription initiation in vitro, suggesting that the two proteins may have a common role in this fundamental process.

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The expression of polymerase gamma and mitochondrial transcription factor A and the regulation of mitochondrial DNA content in mature human sperm

Human Reproduction ◽

10.1093/humrep/dem030 ◽

2007 ◽

Vol 22 (6) ◽

pp. 1585-1596 ◽

Cited By ~ 83

Author(s):

Alexandra Amaral ◽

João Ramalho-Santos ◽

Justin C. St John

Keyword(s):

Transcription Factor ◽

Mitochondrial Dna ◽

Dna Content ◽

Human Sperm ◽

Mitochondrial Transcription ◽

Polymerase Gamma ◽

Mitochondrial Transcription Factor ◽

Mitochondrial Dna Content ◽

Mitochondrial Transcription Factor A

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DrosophilaMitochondrial Transcription Factor B2 Regulates Mitochondrial DNA Copy Number and Transcription in Schneider Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m401643200 ◽

2004 ◽

Vol 279 (26) ◽

pp. 26900-26905 ◽

Cited By ~ 63

Author(s):

Yuichi Matsushima ◽

Rafael Garesse ◽

Laurie S. Kaguni

Keyword(s):

Transcription Factor ◽

Mitochondrial Dna ◽

Copy Number ◽

Dna Copy Number ◽

Mitochondrial Dna Copy Number

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Mitochondrial Transcription Factor A Regulates Mycobacterium bovis–Induced IFN-β Production by Modulating Mitochondrial DNA Replication in Macrophages

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz461 ◽

2019 ◽

Author(s):

Yinjuan Song ◽

Tariq Hussain ◽

Jie Wang ◽

Yi Liao ◽

Ruichao Yue ◽

...

Keyword(s):

Transcription Factor ◽

Mitochondrial Dna ◽

Mycobacterium Bovis ◽

Intracellular Survival ◽

Vital Role ◽

Mitochondrial Transcription ◽

Host Immune Responses ◽

Mitochondrial Transcription Factor ◽

Copy Numbers ◽

Mitochondrial Transcription Factor A

Abstract Background Mycobacterium bovis persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon-β (IFN-β) is one of these critical strategies. The mitochondrial transcription factor A (TFAM) plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-β production in response to viral infection. However, its role in the production of IFN-β by M. bovis has not been elucidated. Methods In the current study, we investigated the role of TFAM in the production of IFN-β in M. bovis–infected macrophages. Results We found that knockdown of TFAM expression significantly reduced M. bovis–induced IFN-β production, mtDNA copy numbers and cytosolic mtDNA were increased in murine macrophages with M. bovis infection, cytosolic mtDNA contributed to IFN-β production, and TFAM was required for the increase in mtDNA copy numbers induced by M. bovis. We also observed that TFAM affected the intracellular survival of M. bovis. Conclusions Our results suggest that TFAM plays an essential role in M. bovis–induced IFN-β production by regulating mtDNA copy numbers. This might be a new strategy adopted by M. bovis for its intracellular survival.

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