New potentials of mitochondrial DNA editing
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EDITORIAL
New potentials of mitochondrial DNA editing Willian Wang & Xiangdong Wang
Received: 15 July 2020 / Accepted: 21 July 2020 # Springer Nature B.V. 2020
Abstract Gene modification and editing using mitochondrial DNA (mtDNA) is a promising option to conventional therapy for mitochondrial dysfunction which can result in a wide range of diseases and failure of organ and tissue functions. RNA-free DddA-derived cytosine base editors have been a promising method due to its high target specificity and high product purity in human mtDNA. However, mtDNA editing is still only a promising option and further studies and investigations are required prior to implementing it in different cell types, organelles, and various diseases as a new clinical therapy. Keywords mtDNA . Genes . Editing . Mitochondria
Mitochondria play important roles in the maintenance of organ/tissue function in the body by mitochondrial genetic messaging, energy production, and metabolism. Mitochondrial dysfunction is responsible for the development of cell metabolism disorders, tissue edema and injury, diseases, cell resistance against drugs, and genetic heterogeneity (Fang et al. 2019; Gutierrez et al. 2019; Hasnat et al. 2019). Of those mitochondrial elements, mitochondrial DNA (mtDNA) is crucial in the communication with nuclear messages, organelles, and cells, as well as regulating cell response, autophagy/mitophagy, genome activation, and cell interaction (Wu et al. 2018). mtDNA is a W. Wang : X. Wang (*) Zhongshan Hospital Institute of Clinical Science, Fudan University Shanghai Medical College, Shanghai, China e-mail: [email protected]
control center for mitochondrial-epigenetic crosstalk, the occurrence of mitophagy, desensitization of targeted therapy, and dysfunction of mitochondrial respiratory megacomplexes. The stability of mtDNA is maintained and regulated by methylation of mtDNA, mtDNA methylation-associated networks and factors, methyltransferases, nucleotides, mt-rRNAs, and other epigenetic modifications. Defining mitochondrial functions was considered to be a milestone, and developing a better understanding of how genome DNA and mtDNA interacts, their intracellular signaling pathways, patient phenomes, and mtDNA is crucial in developing methods for DNA editing (Wang et al. 2020a). Functional profiles and regulations of mtDNA methylation are dependent upon the number of s control region sites for methylation, which enzymes and regulators are involved, and the differentiation among cell types, species, functions, and diseases. In addition, targeted gene editing of mtDNA can provide new insights for understanding novel functions of mtDNA and for developing new therapies for human maternally inherent mitochondrial diseases or other diseases. The aims of this editorial are to briefly overview the recent development of mtDNA editing/modification and to call special attention to exploring new potential venues for mtDNA therapy. Mitochondrial heteroplasmy is a factor influencing the stability and function of mtDNA by altering the copy
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