Article
Clinical Neurology
Carola Hedberg-Oldfors, Ulrika Lindgren, Swaraj Basu, Kittichate Visuttijai, Christopher Lindberg, Maria Falkenberg, Erik Larsson Lekholm, Anders Oldfors
Summary: Deep sequencing and quantitation of mtDNA variants in muscle samples from IBM patients and controls revealed significantly increased levels of large deletions and duplications in IBM muscles, as well as indications of increased somatic single nucleotide variants and reduced mtDNA copy numbers compared to controls. The distribution and types of variants were similar in IBM muscle and controls, suggesting an accelerated aging process in IBM muscle possibly associated with chronic inflammation.
Article
Biochemistry & Molecular Biology
Ruby Zelissen, Somaieh Ahmadian, Joaquin Montilla-Rojo, Erika Timmer, Monique Ummelen, Anton Hopman, Hubert Smeets, Florence van Tienen
Summary: Mitochondrial DNA (mtDNA) mutations are found to be the cause of mitochondrial myopathies in 25% of patients. Lowering the mutation load can reduce disease manifestations, and this study demonstrates the potential of fusing wild-type mesoangioblasts with mtDNA mutant myotubes to achieve this. The researchers successfully reduced the mtDNA mutation load in vitro by fusing wild-type mesoangioblasts with myotubes containing specific mtDNA mutations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Yun Li, Xiaohuan Xia, Yi Wang, Jialin C. Zheng
Summary: This review summarizes the latest progress on the relationship between mitochondrial dysfunction and microglial activation in AD, highlighting the importance of studying this relationship and potential therapeutic strategies.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Medicine, Research & Experimental
Direnis Erdinc, Alejandro Rodriguez-Luis, Mahmoud R. Fassad, Sarah Mackenzie, Christopher M. Watson, Sebastian Valenzuela, Xie Xie, Katja E. Menger, Kate Sergeant, Kate Craig, Sila Hopton, Gavin Falkous, Joanna Poulton, Hector Garcia-Moreno, Paola Giunti, Carlos A. de Moura Aschoff, Jonas A. Morales Saute, Amelia J. Kirby, Camilo Toro, Lynne Wolfe, Danica Novacic, Lior Greenbaum, Aviva Eliyahu, Ortal Barel, Yair Anikster, Robert McFarland, Grainne S. Gorman, Andrew M. Schaefer, Claes M. Gustafsson, Robert W. Taylor, Maria Falkenberg, Thomas J. Nicholls
Summary: TOP3A is an enzyme responsible for removing torsional strain and interlinks between DNA molecules. Pathogenic variants in TOP3A can cause a disorder similar to Bloom syndrome, while bi-allelic variants result in an adult-onset mitochondrial disease with specific clinical characteristics. The severity of the TOP3A catalytic defect determines the clinical outcome, with milder variants causing the adult-onset mitochondrial disease and more severe variants leading to a Bloom-like syndrome with mitochondrial dysfunction in childhood.
EMBO MOLECULAR MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Martin Lang, Anne Gruenewald, Peter P. Pramstaller, Andrew A. Hicks, Irene Pichler
Summary: Mitochondria play important roles in neurodegenerative diseases like Parkinson's disease (PD). The contribution of mtDNA variants to PD pathogenesis is still debated, but studies have shown evidence of mtDNA variants in cybrid cell models contributing to the PD phenotype.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
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
Cardiac & Cardiovascular Systems
Katherine Margaret Cheema, Ed Dicks, Jeremy Pearson, Nilesh J. Samani
Summary: The British Heart Foundation's annual statistical compendium provides comprehensive and accessible epidemiological data on cardiovascular disease (CVD) in the UK. The study shows a consistent decline in CVD mortality in the UK over recent decades, but inequalities in mortality rates still exist among the UK nations. The use of primary prevention medications and interventional procedures has contributed to the improvement in mortality rates. CVD remains a significant burden in terms of morbidity and economic impact. The study emphasizes the importance of reliable statistics and the BHF's annual compendium in understanding the burden of CVD and identifying opportunities for future research.
CARDIOVASCULAR RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Natalya Kozhukhar, Mikhail F. Alexeyev
Summary: Researchers used the GeneSwap approach to analyze the contributions of the TFAM C-terminal domain to mtDNA transcription and replication. They found that tail-less TFAM supports both mtDNA replication and transcription, and mutations in TFAM impair HSP1 transcription to a greater extent than LSP transcription. These findings suggest the need for further refinement of the current model of mtDNA transcription.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Legal
Jennifer A. McElhoe, Peter R. Wilton, Walther Parson, Mitchell M. Holland
Summary: This study analyzed 1301 control region sequences to assess the frequency of point heteroplasmy in different populations. The majority of heteroplasmic individuals had only one heteroplasmic site and the observed heteroplasmies were relatively low in frequency across nucleotide positions. The posterior frequency estimates provided a conservative statistical framework for evaluating haplotype/heteroplasmy matches in forensic cases.
INTERNATIONAL JOURNAL OF LEGAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Junfan Guo, Wenxia Yu, Min Li, Hongyu Chen, Jie Liu, Xiaowen Xue, Jianxiang Lin, Shisheng Huang, Wenjie Shu, Xingxu Huang, Zhen Liu, Shengqi Wang, Yunbo Qiao
Summary: We identified a dsDNA deaminase from Roseburia intestinalis and generated CRISPR-mediated nuclear and mitochondrial CBEs that can perform C-to-T editing at both HC and GC targets. The efficiency of nuclear and mtDNA editing was significantly improved by fusing transactivators to the tail of DddAtox- or riDddAtox-mediated CBEs. We successfully stimulated disease-associated mtDNA mutations in cultured cells and mouse embryos with high conversion frequencies using riDddAtox-based and Rta-assisted mitoCBEs.
Review
Clinical Neurology
Amica C. Muller-Nedebock, Francois H. van Der Westhuizen, Sulev Koks, Soraya Bardien
Summary: Mitochondrial dysfunction plays a central role in Parkinson's disease pathogenesis, particularly affecting dopaminergic neurons. Variations and depletion of mtDNA in mitochondria can lead to inadequate energy production, contributing to the onset of disease phenotype. Studies suggest that nuclear-encoded genes associated with mtDNA processes may influence PD risk by disrupting mtDNA processes or impairing their regulation.
MOVEMENT DISORDERS
(2021)
Article
Mathematics
Francisca Corpas-Burgos, Miguel A. Martinez-Beneito
Summary: The use of spatio-temporal disease mapping for forecasting spatial distribution of diseases relies on various modeling tools and methods. This study introduces an enhanced autoregressive spatio-temporal model with a common spatial component, showing improved predictive capabilities compared to the original model, as illustrated through a comprehensive study on mortality data sets in the Valencian Region of Spain.
Article
Cell Biology
Natalya Kozhukhar, Mikhail F. Alexeyev
Summary: TFAM from chickens cannot support the replication of human mitochondrial DNA, but can support respiration. Variants obtained by modifying TFAM can complement each other's deficiencies. A novel mode of regulating respiratory chain biogenesis has also been discovered.
Review
Cell Biology
Arianna Manini, Elena Abati, Giacomo Pietro Comi, Stefania Corti, Dario Ronchi
Summary: Maintenance of mitochondrial DNA homeostasis is crucial for preserving the structural and functional integrity of mtDNA molecules. Mutations in certain nuclear genes can impair mtDNA maintenance and lead to clinical syndromes characterized by mtDNA depletion or deletions. Studies have shown a progressive accumulation of mtDNA deletions in dopaminergic neurons of elderly individuals and Parkinson's disease patients, with parkinsonism often observed in mtDNA instability syndromes. Several genes related to Parkinson's disease, such as PARK2 and LRRK2, play a role in mtDNA maintenance. Various mouse models have provided in vivo evidence of the importance of mtDNA stability for nigrostriatal integrity.
AGEING RESEARCH REVIEWS
(2022)
Review
Clinical Neurology
Isabelle K. Gorham, Robert C. Barber, Harlan P. Jones, Nicole R. Phillips
Summary: Literature suggests that the release of mtDNA in Alzheimer's disease is correlated with increased immune responses, indicating its potential as a biomarker. However, there are still unanswered questions and further research in this area is needed.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Iain G. Johnston
Review
Genetics & Heredity
Juvid Aryaman, Iain G. Johnston, Nick S. Jones
FRONTIERS IN GENETICS
(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)
Article
Biochemistry & Molecular Biology
Sam F. Greenbury, Mauricio Barahona, Iain G. Johnston
Article
Cell Biology
Iain G. Johnston
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2019)
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.
Article
Health Care Sciences & Services
Iain G. Johnston, Till Hoffmann, Sam F. Greenbury, Ornella Cominetti, Muminatou Jallow, Dominic Kwiatkowski, Mauricio Barahona, Nick S. Jones, Climent Casals-Pascual
NPJ DIGITAL MEDICINE
(2019)