Human mitochondrial nucleases. (1st February 2017)

• Record Type: Journal Article
• Authors: Bruni, Francesco; Lightowlers, Robert N.; Chrzanowska‐Lightowlers, Zofia M.
• Is Part Of: FEBS journal. Volume 284:Number 12(2017)
• Page Start: 1767
• Page End: 1777
• Publication Date: 2017-02-01
• Subjects: cleavage -- degradation -- human -- mtDNA -- mitochondria -- mtRNA -- nucleases -- processing; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.13981
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : We illustrate the consequences of using different nucleases to target mutant mitochondrial DNA. Wild‐type mtDNA is depicted in blue and mutant mtDNA is depicted in red with 'x' indicating the presence of a mutation. The change in levels of heteroplasmy affects the clinical and biochemical phenotype. Abstract : Mitochondria are cytosolic organelles that have many essential roles including ATP production via oxidative phosphorylation, apoptosis, iron‐sulfur cluster biogenesis, heme and steroid synthesis, calcium homeostasis, and regulation of cellular redox state. One of the unique features of these organelles is the presence of an extrachromosomal mitochondrial genome (mtDNA), together with all the machinery required to replicate and transcribe mtDNA. The accurate maintenance of mitochondrial gene expression is essential for correct organellar metabolism, and is in part dependent on the levels of mtDNA and mtRNA, which are regulated by balancing synthesis against degradation. It is clear that although a number of mitochondrial nucleases have been identified, not all those responsible for the degradation of DNA or RNA have been characterized. Recent investigations, however, have revealed the contribution that mutations in the genes coding for these enzymes has made to causing pathogenic mitochondrial diseases.