Abstract:Mitochondrial topoisomerase I is a genetically distinct mitochondria-dedicated enzyme with a crucial but so far unknown role in the homeostasis of mitochondrial DNA metabolism. Here, we present data suggesting a negative regulatory function in mitochondrial transcription or transcript stability. Deficiency or depletion of mitochondrial topoisomerase I increased mitochondrial transcripts, whereas overexpression lowered mitochondrial transcripts, depleted respiratory complexes I, III and IV, decreased cell respi… Show more
“…Mitochondria from mammalian fibroblasts contain a specific DNA topoisomerase, topoisomerase I. Sobek et al (52) report increased transcription of respiratory chain mitochondrial genes when DNA topoisomerase I is either deficient or depleted. It is concluded that topoisomerase I inhibits mitochondrial DNA transcription and that release of transcriptional inhibition is accompanied by increased respiratory rate and superoxide production (52).…”
Section: Experimental Evidence Bearing Directly On Corr Evidence 1: Smentioning
confidence: 99%
“…It is concluded that topoisomerase I inhibits mitochondrial DNA transcription and that release of transcriptional inhibition is accompanied by increased respiratory rate and superoxide production (52). DNA topoisomerase is also implicated in redox control of transcription of mitochondrial DNA in plant tissue (53).…”
Section: Experimental Evidence Bearing Directly On Corr Evidence 1: Smentioning
Chloroplasts and mitochondria are subcellular bioenergetic organelles with their own genomes and genetic systems. DNA replication and transmission to daughter organelles produces cytoplasmic inheritance of characters associated with primary events in photosynthesis and respiration. The prokaryotic ancestors of chloroplasts and mitochondria were endosymbionts whose genes became copied to the genomes of their cellular hosts. These copies gave rise to nuclear chromosomal genes that encode cytosolic proteins and precursor proteins that are synthesized in the cytosol for import into the organelle into which the endosymbiont evolved. What accounts for the retention of genes for the complete synthesis within chloroplasts and mitochondria of a tiny minority of their protein subunits? One hypothesis is that expression of genes for protein subunits of energy-transducing enzymes must respond to physical environmental change by means of a direct and unconditional regulatory control—control exerted by change in the redox state of the corresponding gene product. This hypothesis proposes that, to preserve function, an entire redox regulatory system has to be retained within its original membrane-bound compartment. Colocation of gene and gene product for redox regulation of gene expression (CoRR) is a hypothesis in agreement with the results of a variety of experiments designed to test it and which seem to have no other satisfactory explanation. Here, I review evidence relating to CoRR and discuss its development, conclusions, and implications. This overview also identifies predictions concerning the results of experiments that may yet prove the hypothesis to be incorrect.
“…Mitochondria from mammalian fibroblasts contain a specific DNA topoisomerase, topoisomerase I. Sobek et al (52) report increased transcription of respiratory chain mitochondrial genes when DNA topoisomerase I is either deficient or depleted. It is concluded that topoisomerase I inhibits mitochondrial DNA transcription and that release of transcriptional inhibition is accompanied by increased respiratory rate and superoxide production (52).…”
Section: Experimental Evidence Bearing Directly On Corr Evidence 1: Smentioning
confidence: 99%
“…It is concluded that topoisomerase I inhibits mitochondrial DNA transcription and that release of transcriptional inhibition is accompanied by increased respiratory rate and superoxide production (52). DNA topoisomerase is also implicated in redox control of transcription of mitochondrial DNA in plant tissue (53).…”
Section: Experimental Evidence Bearing Directly On Corr Evidence 1: Smentioning
Chloroplasts and mitochondria are subcellular bioenergetic organelles with their own genomes and genetic systems. DNA replication and transmission to daughter organelles produces cytoplasmic inheritance of characters associated with primary events in photosynthesis and respiration. The prokaryotic ancestors of chloroplasts and mitochondria were endosymbionts whose genes became copied to the genomes of their cellular hosts. These copies gave rise to nuclear chromosomal genes that encode cytosolic proteins and precursor proteins that are synthesized in the cytosol for import into the organelle into which the endosymbiont evolved. What accounts for the retention of genes for the complete synthesis within chloroplasts and mitochondria of a tiny minority of their protein subunits? One hypothesis is that expression of genes for protein subunits of energy-transducing enzymes must respond to physical environmental change by means of a direct and unconditional regulatory control—control exerted by change in the redox state of the corresponding gene product. This hypothesis proposes that, to preserve function, an entire redox regulatory system has to be retained within its original membrane-bound compartment. Colocation of gene and gene product for redox regulation of gene expression (CoRR) is a hypothesis in agreement with the results of a variety of experiments designed to test it and which seem to have no other satisfactory explanation. Here, I review evidence relating to CoRR and discuss its development, conclusions, and implications. This overview also identifies predictions concerning the results of experiments that may yet prove the hypothesis to be incorrect.
“…Some drugs have been reported to deplete mitochondrial DNA by interfering with mitochondrial DNA polymerase gamma activity (Rowe et al, 2001;Neuzil et al, 2013). Top1mt is also important for mitochondrial homeostasis (Douarre et al, 2012), mtDNA replication (Zhang and Pommier, 2008), mtDNA transcription (Sobek et al, 2013), and mtDNA integrity (Medikayala et al, 2011). Yet, there are no drugs known to specifically target Top1mt.…”
Section: Discussionmentioning
confidence: 99%
“…Unlike TOP2Β (Low et al, 2003) and TOP3Α, TOP1mt is the only topoisomerase gene coding for a single polypeptide solely targeted to mitochondria (Zhang et al, 2001;Chinnery and Hudson, 2013). In addition to studying Top1mt's roles in regulating mtDNA replication (Zhang and Pommier, 2008), transcription (Sobek et al, 2013), and mtDNA integrity (Medikayala et al, 2011), it has become possible to examine Top1mt functions genetically. Murine embryonic fibroblasts generated from TOP1mt knockout mice exhibit mitochondrial defects with marked increase in reactive oxygen species production, calcium signaling, hyperpolarization of mitochondrial membranes, and increased mitophagy (Douarre et al, 2012).…”
“…The rate-limiting enzyme in catecholamine synthesis, which is TH, indicates a selective increase in TH mRNA (mitochondria ribosomal nuclear atom). This is normally accompanied by a corresponding response in immune reactive TH protein owing to various stressors in the environment (Blanchard et al, 2001;Sobek et al, 2013;Janska & Kwasniak, 2014).…”
Section: Catecholamines Cortisol and Glucocorticoidsmentioning
Increased public concern for animal welfare in the logistics chain has led to a rise in the scrutiny of the treatment of food animals. Factors affecting the status of welfare of slaughter animals begin at the farm and occur during transportation and at the abattoir. The activities that animals pass through before slaughter are thought to have negative effects on both the animal and the product. Before or during this period, animals suffer pain, which compromises their physical, health and biochemical status, and meat quality and quantity; which leads to economic losses. Environmental impact plays a role in the behaviour, growth, development and welfare of animals, even though it is associated with the production of greenhouse gases and biodiversity. Food producers are also mindful of the challenges of feeding the ever-increasing human population. Although the issues of animal production, which range from the environment to human health, have been discussed, animal welfare-related factors that are at play in the production chain of farm animals must still be addressed. An understanding of the animal's environment, behaviour and the biochemical interactions that are at play in stressful conditions; and the implications of these for animal health and welfare are key to developing effective mitigation strategies. Therefore, the objective of this review is to highlight the literature on animal welfare, and suggest strategies that could be adopted for the improvement of meat animals, meat quality and meat products. ______________________________________________________________________________________
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