Review
Medicine, Research & Experimental
Vladislav O. Soldatov, Marina V. Kubekina, Marina Yu. Skorkina, Andrei E. Belykh, Tatiana V. Egorova, Mikhail V. Korokin, Mikhail V. Pokrovskiy, Alexey V. Deykin, Plamena R. Angelova
Summary: Mitochondrial diseases are a diverse group of multisystem disorders involving metabolic errors. Understanding mitochondrial genetics is crucial for developing treatment strategies for rare and difficult-to-diagnose diseases.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hansi Weissensteiner, Lukas Forer, Liane Fendt, Azin Kheirkhah, Antonio Salas, Florian Kronenberg, Sebastian Schoenherr
Summary: haplocheck is a tool that accurately detects sample contamination in mitochondrial studies, especially in large-scale datasets, without being affected by phylogenetic distance. It is available as a command-line tool and cloud web service for easy access to interactive reports.
Review
Genetics & Heredity
Jose Domingo Barrera-Paez, Carlos T. Moraes
Summary: Manipulating the mitochondrial genome has been challenging due to its double membranes and lack of a robust recombination system. However, advancements in specific nucleases and gene-editing platforms have allowed researchers to selectively eliminate mutant genes and precisely modify mtDNA in animal cells, representing major progress.
TRENDS IN GENETICS
(2022)
Article
Multidisciplinary Sciences
Ugne Zekonyte, Sandra R. Bacman, Jeff Smith, Wendy Shoop, Claudia Pereira, Ginger Tomberlin, James Stewart, Derek Jantz, Carlos T. Moraes
Summary: This study shows the potential of using mitoARCUS, a mitochondrial-targeted gene editing platform, to specifically eliminate mutant mtDNA with a m.5024C>T mutation in the mt-tRNA(Ala) gene. MitoARCUS was successful in robustly eliminating mutant mtDNA in the liver and skeletal muscle of mice, demonstrating its promise as a powerful tool for the treatment of heteroplasmic mitochondrial DNA mutations.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Carlos Jhovani Perez-Amado, Amellalli Bazan-Cordoba, Alfredo Hidalgo-Miranda, Silvia Jimenez-Morales
Summary: Analysis of mitochondrial genome is important in studying human diseases, including cancer, as mutations and variants in tumors impact tumor growth and invasion. Heteroplasmy-shifting is suggested to play a role in tumor progression and treatment response, but further research is needed to fully understand its clinical implications in treating human cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Wendy K. Shoop, Janel Lape, Megan Trum, Alea Powell, Emma Sevigny, Adam Mischler, Sandra R. Bacman, Flavia Fontanesi, Jeff Smith, Derek Jantz, Cassandra L. Gorsuch, Carlos T. Moraes
Summary: This study developed a mitochondrial-targeted nuclease called mitoARCUS to target the common pathogenic mtDNA mutation m.3243A>G. mitoARCUS efficiently eliminated mutant mtDNA without affecting wild-type mtDNA, leading to improvements in mitochondrial protein steady-state levels and respiration. In vivo experiments using an adeno-associated virus delivery system in a m.3243A>G xenograft mouse model demonstrated the efficacy of mitoARCUS. These findings support the development of mitoARCUS as a gene-editing therapeutic for m.3243A>G-associated diseases.
Article
Biochemistry & Molecular Biology
Agnieszka Piotrowska-Nowak, Krzysztof Safranow, Jakub G. Adamczyk, Ireneusz Soltyszewski, Pawel Cieszczyk, Katarzyna Tonska, Cezary Zekanowski, Beata Borzemska
Summary: Energy efficiency is crucial for athletic performance. This study investigated the relationship between mitochondrial DNA (mtDNA) variants and athletic performance among Polish male athletes. The analysis revealed no correlation between mtDNA variants and athletic performance, but showed a lower mtDNA copy number in both power and endurance athletes compared to controls.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Alessia Di Donfrancesco, Giulia Massaro, Ivano Di Meo, Valeria Tiranti, Emanuela Bottani, Dario Brunetti
Summary: This article provides a comprehensive overview of the application of gene therapy in mitochondrial diseases (MDs), addressing the main challenges, feasible solutions, and future prospects.
Review
Biochemistry & Molecular Biology
Bibekananda Kar, Santiago R. Castillo, Ankit Sabharwal, Karl J. Clark, Stephen C. Ekker
Summary: Mitochondria are crucial organelles involved in energy generation and cell functionality, as well as producing important signaling molecules. They can vary between cells, tissues, and organs, and undergo changes due to disease, aging, and environmental factors. Human mitochondrial DNA can have single nucleotide variants that are linked to life-threatening diseases. Mitochondrial DNA base editing tools have proven useful in creating disease models and offer potential for personalized gene therapies targeting mtDNA-based disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Mohammed Dashti, Hussain Alsaleh, Juan L. Rodriguez-Flores, Muthukrishnan Eaaswarkhanth, Fahd Al-Mulla, Thangavel Alphonse Thanaraj
Summary: The study revealed that individuals with mitochondrial haplogroup J in the Qatari population have an increased risk of obesity, while individuals with haplogroup X have a lower risk of obesity. Additionally, a set of 38 mitochondrial variants were found to be associated with obesity.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Maria Angela Diroma, Alessandra Modi, Martina Lari, Luca Sineo, David Caramelli, Stefania Vai
Summary: The study successfully reconstructed almost complete mtDNA genomes for most analyzed samples, and provided guidelines for dealing with potential artifact sources. Through data simulations, it was demonstrated that new sequencing technologies and software are sensitive enough to detect partially mutated sites in ancient genomes and discriminate true variants from artifacts.
FRONTIERS IN GENETICS
(2021)
Review
Endocrinology & Metabolism
James Bruce Stewart
Summary: Mitochondrial disorders, a class of heritable diseases, can manifest in various ways and at different stages of life. While nuclear DNA plays a vital role in these diseases, mutations in the mtDNA can also cause heritable conditions. Animal models for studying these diseases have been rare due to challenges in editing animal mtDNA.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Chemistry, Multidisciplinary
Huaixin Zhao, Zhili Zhang, Duo Zuo, Linghui Li, Feng Li, Dayong Yang
Summary: A DNA-polydopamine-MnO2 nanocomplex was developed for near-infrared light-powered catalytic activity of DNAzyme in vivo. The complex can enhance Egr-1 mRNA cleavage activity of DNAzyme, leading to downregulation of Egr-1 protein in tumor cells and achieving a synergistic tumor ablation effect through heat stress induction.
Article
Genetics & Heredity
Liyan Xu, Kaili Yang, Qi Fan, Yuwei Gu, Shengwei Ren
Summary: This study characterized the mtDNA heteroplasmy profile in KC and found an association between heteroplasmic levels of m.16180_16181delAA and KC.
FRONTIERS IN GENETICS
(2023)
Review
Pharmacology & Pharmacy
Ruben Faria, Prisca Boisguerin, Angela Sousa, Diana Costa
Summary: Mitochondria are crucial cellular organelles responsible for energy production in cells, and mutations in their DNA (mtDNA) can lead to various diseases. Mitochondrial gene therapy is a promising strategy to address these disorders. Developing efficient mtDNA-based delivery systems to target and transfect mammalian mitochondria is an exciting area of research that can contribute to restoring normal mitochondrial function.