Review
Biochemistry & Molecular Biology
Mengmeng Liu, Wei Ji, Xin Zhao, Xiaoliang Liu, Ji-Fan Hu, Jiuwei Cui
Summary: Mitochondrial diseases are caused by mutations in genes involved in mitochondrial oxidative phosphorylation, and the severity of disorders is related to the degree of gene mutation. Current clinical treatments focus on symptomatic management, but replacing or repairing dysfunctional mitochondria may be an effective approach. Recent progress has been made in gene therapies that overcome limitations, including mitochondrial replacement therapy, genome manipulation, nucleotide programming, DNA editing, and RNA interference.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Yuko Takeda, Louise Hyslop, Meenakshi Choudhary, Fiona Robertson, Angela Pyle, Ian Wilson, Mauro Santibanez-Koref, Douglass Turnbull, Mary Herbert, Gavin Hudson
Summary: Mitochondrial replacement technology (MRT) aims to reduce the risk of disease in children born to women with pathogenic mitochondrial DNA (mtDNA) variants. Haplogroup matching between egg donors and women undergoing MRT has been proposed, but this study finds that it would limit the availability of donors and does not necessarily reduce mtDNA sequence divergence between donor/recipient pairs.
Article
Biochemistry & Molecular Biology
Ramin Abdoli, Tarikul Huda Mazumder, Shahla Nematollahian, Reza Sourati Zanjani, Rahim Abdollahi Mesbah, Arif Uddin
Summary: This study compared the mitochondrial genomes of different types of silkworms and found relationships between codon usage bias, genetic similarity, and phylogenetics. Results showed that the genomes had higher AT content than GC content and codons with A or T endings were over-represented. The codon usage bias of mitochondrial genes was influenced by both natural selection and mutation pressure, with natural selection playing a larger role. In addition, the mitochondrial genomes of Bombyx mori and Bombyx mandarina were most similar, while the COX1, COX2, and COX3 genes showed the most differences.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Obstetrics & Gynecology
Hong Ma, Crystal Van Dyken, Hayley Darby, Aleksei Mikhalchenko, Nuria Marti-Gutierrez, Amy Koski, Dan Liang, Ying Li, Rebecca Tippner-Hedges, Eunju Kang, Yeonmi Lee, Heather Sidener, Cathy Ramsey, Travis Hodge, Paula Amato, Shoukhrat Mitalipov
Summary: The study found that the long-term effects of mitochondrial replacement therapy (MRT) in monkeys showed no significant differences in growth, general health, and fertility compared to controls. While some monkeys showed increased levels of maternal or paternal mtDNA contributions in certain tissues and organs, overall, MRT did not cause adverse effects and was compatible with normal postnatal development in nonhuman primates. More clinical trials are needed to fully assess the safety and effectiveness of MRT in humans.
HUMAN REPRODUCTION
(2021)
Review
Genetics & Heredity
James B. Stewart, Patrick F. Chinnery
Summary: Deep resequencing has revealed extreme genetic variation in mitochondrial genomes at multiple levels, shedding light on the origins of human mitochondrial DNA mutations and their impact on rare and common human diseases, including cancer.
NATURE REVIEWS GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Sanjana Saravanan, Caitlin J. Lewis, Bhavna Dixit, Matthew S. O'Connor, Alexandra Stolzing, Amutha Boominathan
Summary: This review discusses the various pathologies caused by mtDNA mutations and evaluates current therapeutic approaches. The potential value of allotopic expression as a gene therapy method for restoring mitochondrial health is highlighted.
Review
Biochemistry & Molecular Biology
Jun Feng, Zhaowei Chen, Wei Liang, Zhongping Wei, Guohua Ding
Summary: The kidney, which is a mitochondria-rich organ, is affected by mitochondria-related pathologies. Damage to mitochondrial DNA (mtDNA) plays a role in kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). MtDNA damage is closely associated with loss of kidney function, and the levels of mtDNA in peripheral serum and urine can reflect kidney injury. Alleviating mtDNA damage can promote mitochondrial function recovery and reduce kidney injury. Therefore, mtDNA damage may serve as a novel biomarker for assessing kidney injury and provide a new therapeutic option for kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mariceli Baia Leao Barros, Danilo do Rosario Pinheiro, Barbara do Nascimento Borges
Summary: Glioblastoma (GBM) is a highly aggressive tumor originating from neural stem cells of the central nervous system, with mutations in mitochondrial DNA (mtDNA) leading to mitochondrial dysfunction, playing a crucial role in GBM pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Yang Chen, Wei-jia Wu, Li-wei Xing, Xiao-juan Zhang, Jing Wang, Xiao-yan Xia, Rui Zhao, Rong Zhao
Summary: This study examined the correlations between mtDNA D-loop, its haplotypes, and PCOS in the Chinese population, and found that certain mtDNA D-loop mutations and haplotypes may confer protection against PCOS in Chinese women. In addition, elevated mtDNA copy number may serve as an indicator during early stages of PCOS.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Genevieve Trombly, Afaf Milad Said, Alexei P. Kudin, Viktoriya Peeva, Janine Altmueller, Kerstin Becker, Karl Koehrer, Gabor Zsurka, Wolfram S. Kunz
Summary: The study investigated the effects of hydrogen peroxide on mitochondrial DNA integrity. The results showed that hydrogen peroxide treatment resulted in DNA breaks, which were then repaired through rapid repair of single-strand breaks and degradation of double-strand breaks-generated linear fragments. Inactivation of mitochondrial DNA degradation resulted in the persistence of linear fragments in mutant cells without affecting the repair of single-strand breaks. These findings highlight the interplay between DNA repair and degradation processes, and the potential generation of somatic mitochondrial DNA deletions.
Article
Biology
Alessandro Formaggioni, Andrea Luchetti, Federico Plazzi
Summary: Mitochondrial genomes exhibit a bewildering diversity in structure, architecture, gene content, and functionality; different taxa show distinct characteristics in their mitochondrial genomes, with variations in gene number and composition.
Review
Biochemistry & Molecular Biology
Siyang Liao, Li Chen, Zhiyin Song, He He
Summary: Mitochondrion is an organelle responsible for cellular respiration and ATP production. Its DNA, known as mtDNA, encodes essential subunits of respiratory complexes and can be damaged, leading to mitochondrial dysfunction and diseases. Cells employ multiple pathways to repair and remove damaged mtDNA in order to maintain mitochondrial quality and cellular homeostasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Boris Pantic, Daniel Ives, Mara Mennuni, Diego Perez-Rodriguez, Uxoa Fernandez-Pelayo, Amaia Lopez de Arbina, Mikel Munoz-Oreja, Marina Villar-Fernandez, Thanh-mai Julie Dang, Lodovica Vergani, Iain G. Johnston, Robert D. S. Pitceathly, Robert McFarland, Michael G. Hanna, Robert W. Taylor, Ian J. Holt, Antonella Spinazzola
Summary: By restricting the availability of glucose and glutamine, the authors have demonstrated that functional mitochondrial DNAs can be propagated while pathological variants are suppressed. The study shows that 2-Deoxy-D-glucose inhibits the replication of mutant mtDNA and glutamine withdrawal suppresses mtDNA synthesis in mutant cells. This highlights the importance of mitochondrial fitness in driving metabolite preference for mtDNA replication, offering potential interventions to suppress pathological mtDNAs.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Haixin Zhang, Marco Esposito, Mikael G. Pezet, Juvid Aryaman, Wei Wei, Florian Klimm, Claudia Calabrese, Stephen P. Burr, Carolina H. Macabelli, Carlo Viscomi, Mitinori Saitou, Marcos R. Chiaratti, James B. Stewart, Nick Jones, Patrick F. Chinnery
Summary: Heteroplasmic mitochondrial DNA mutations play a significant role in inherited diseases, with a few recurrent mutations accounting for the majority of cases. The preferential transmission of these mutations and their maintenance at various levels may be key factors contributing to disease development.
Review
Biochemistry & Molecular Biology
Margit Heiske, Omar Alva, Veronica Pereda-Loth, Matthew Van Schalkwyk, Chantal Radimilahy, Thierry Letellier, Jean-Aime Rakotarisoa, Denis Pierron
Summary: The origin of the Malagasy population has long been speculated since the 16th century, with contributions from African, Asian, and other populations suggested based on various research methods. Advances in technology and genetic research have provided more insights into the origin of the Malagasy population.
HUMAN MOLECULAR GENETICS
(2021)
Article
Biochemistry & Molecular Biology
Matthew D. B. Jackson, Salva Duran-Nebreda, Daniel Kierzkowski, Soeren Strauss, Hao Xu, Benoit Landrein, Olivier Hamant, Richard S. Smith, Iain G. Johnston, George W. Bassel
Article
Genetics & Heredity
Juvid Aryaman, Charlotte Bowles, Nick S. Jones, Iain G. Johnston
Article
Multidisciplinary Sciences
Clare Ziegler, Rosemary J. Dyson, Iain G. Johnston
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2019)
Article
Biochemical Research Methods
Hanne Hoitzing, Payam A. Gammage, Lindsey van Haute, Michal Minczuk, Iain G. Johnston, Nick S. Jones
PLOS COMPUTATIONAL BIOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Iain G. Johnston, Joerg P. Burgstaller
BIOCHEMICAL SOCIETY TRANSACTIONS
(2019)
Article
Biochemistry & Molecular Biology
Sam F. Greenbury, Mauricio Barahona, Iain G. Johnston
Article
Genetics & Heredity
Angelos-Theodoros Athanasiou, Thomas Nussbaumer, Stefan Kummer, Martin Hofer, Iain G. Johnston, Moritz Staltner, Daniela M. Allmer, Milcah C. Scott, Claus Vogl, Joelle M. Fenger, Jaime F. Modiano, Ingrid Walter, Ralf Steinborn
JOURNAL OF MOLECULAR MEDICINE-JMM
(2020)
Article
Multidisciplinary Sciences
Salva Duran-Nebreda, Iain G. Johnston, George W. Bassel
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2020)
Article
Biochemistry & Molecular Biology
Ellen C. Royrvik, Iain G. Johnston
NUCLEIC ACIDS RESEARCH
(2020)
Article
Multidisciplinary Sciences
Ana Victoria Lechuga-Vieco, Ana Latorre-Pellicer, Iain G. Johnston, Gennaro Prota, Uzi Gileadi, Raquel Justo-Mendez, Rebeca Acin-Perez, Raquel Martinez-de-Mena, Jose Maria Fernandez-Toro, Daniel Jimenez-Blasco, Alfonso Mora, Jose A. Nicolas-Avila, Demetrio J. Santiago, Silvia G. Priori, Juan Pedro Bolanos, Guadalupe Sabio, Luis Miguel Criado, Jesus Ruiz-Cabello, Vincenzo Cerundolo, Nick S. Jones, Jose Antonio Enriquez
Article
Multidisciplinary Sciences
Iain G. Johnston, Ellen C. Royrvik
Article
Ecology
Arunas Radzvilavicius, Sean Layh, Matthew D. Hall, Damian K. Dowling, Iain G. Johnston
Summary: The interplay between nuclear and mitochondrial genes maintains mitochondrial haplotype diversity within populations, and selects for sex-independent segregation of mitochondrion-interacting genes and for paternal leakage. These effects of genetic linkage evolution can eliminate male-harming fitness effects of mtDNA mutational diversity.
JOURNAL OF EVOLUTIONARY BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Robert L. Peach, Sam F. Greenbury, Iain G. Johnston, Sophia N. Yaliraki, David J. Lefevre, Mauricio Barahona
Summary: This study utilizes a sequence data framework to analyze temporal sequences of task completion in online courses, identifying behaviors, critical tasks, and introducing a probabilistic Bayesian model to predict student performance. The research reveals distinct behaviors within learners, identifies deviations from expected order, explores differences between high and low performing learners, and shows that non-rote learning tasks are correlated with higher performance.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
David M. Edwards, Ellen C. Royrvik, Joanna M. Chustecki, Konstantinos Giannakis, Robert C. Glastad, Arunas L. Radzvilavicius, Iain G. Johnston
Summary: A comprehensive genetic model has been constructed to explain how different mechanisms segregate and decrease damage in organelle DNA (oDNA) across eukaryotes. Gene conversion is identified as a powerful mechanism to increase beneficial cell-to-cell variance without depleting oDNA copy number, explaining the advantage of observed oDNA recombination in diverse organisms. This framework provides insights into how eukaryotes avoid Muller's ratchet and explains the puzzling oDNA differences across taxa.
Article
Biochemistry & Molecular Biology
Joanna M. Chustecki, Daniel J. Gibbs, George W. Bassel, Iain G. Johnston
Summary: This study reveals the tradeoff between physical priorities and "social" priorities of mitochondria dynamics in Arabidopsis, as well as how plant cells resolve this tension to favor efficient networks with high potential for exchanging contents. The combination of physical modeling and experimental data through network analysis sheds light on the fundamental principles underlying complex organelle dynamics.