Article
Multidisciplinary Sciences
Yun Soo Hong, Stephanie L. Battle, Wen Shi, Daniela Puiu, Vamsee Pillalamarri, Jiaqi Xie, Nathan Pankratz, Nicole J. Lake, Monkol Lek, Jerome I. Rotter, Stephen S. Rich, Charles Kooperberg, Alex P. Reiner, Paul L. Auer, Nancy Heard-Costa, Chunyu Liu, Meng Lai, Joanne M. Murabito, Daniel Levy, Megan L. Grove, Alvaro Alonso, Richard Gibbs, Shannon Dugan-Perez, Lukasz P. Gondek, Eliseo Guallar, Dan E. Arking
Summary: Based on the study of participants in the UK Biobank, it was found that mitochondrial heteroplasmy is associated with increased risk of all-cause mortality and the prevalence and incidence of cancer, especially leukemia.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Kathy N. Lam, Peter Spanogiannopoulos, Paola Soto-Perez, Margaret Alexander, Matthew J. Nalley, Jordan E. Bisanz, Renuka R. Nayak, Allison M. Weakley, Feiqiao B. Yu, Peter J. Turnbaugh
Summary: The study demonstrates the use of engineered bacteriophage M13 to deliver DNA to Escherichia coli in the mouse gastrointestinal tract, enabling strain-specific depletion and genomic deletions. Multiple mechanisms allow E. coli to escape targeting, providing a foundation for microbiome editing and suggesting potential for extension to other phage-bacterial pairs.
Article
Surgery
Keshav K. Singh
Summary: The article discusses the genetic and environmental factors contributing to skin aging, highlighting the crucial role of mitochondria in this process. Research suggests that transplanting young mitochondria may potentially rejuvenate aging skin and hair.
PLASTIC AND RECONSTRUCTIVE SURGERY
(2021)
Article
Biology
Darren J. Walsh, David J. Bernard, Faith Pangilinan, Madison Esposito, Denise Harold, Anne Parle-McDermott, Lawrence C. Brody
Summary: The analysis of somatic variation in the mitochondrial genome requires deep sequencing of mitochondrial DNA. This study presents a PCR-free method for ultra-deep sequencing coverage of the mitochondrial genome, using isolated intact mitochondria and a sequence-independent approach. The method avoids false-heteroplasmy calls caused by long-range PCR amplification and enables researchers to identify low frequency heteroplasmy without introducing PCR biases or NUMT contamination.
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Ryan L. Davis, Kishore R. Kumar, Clare Puttick, Christina Liang, Kate E. Ahmad, Fabienne Edema-Hildebrand, Jin-Sung Park, Andre E. Minoche, Velimir Gayevskiy, Amali C. Mallawaarachchi, John Christodoulou, Deborah Schofield, Marcel E. Dinger, Mark J. Cowley, Carolyn M. Sue
Summary: Comprehensive bigenomic sequencing accurately detects causative genetic variants in affected mitochondrial disease patients, providing precise diagnosis, personalized treatment options, and information on genetic transmission risk.
Article
Multidisciplinary Sciences
James de Villiers, Rensu Theart
Summary: This paper presents a novel method using neural networks to predict the occurrence and locations of mitochondrial fission, fusion, and depolarisation events in 3D. The accuracy achieved by the neural networks in predicting these events is relatively low, but it indicates their potential usefulness in the absence of time-lapse sequences. The results of this paper can serve as a baseline for future research in this area.
Article
Cell Biology
Daniela Bebbere, Susanne E. Ulbrich, Katrin Giller, Valeri Zakhartchenko, Horst-Dieter Reichenbach, Myriam Reichenbach, Paul J. Verma, Eckhard Wolf, Sergio Ledda, Stefan Hiendleder
Summary: The study reveals about 50% reduction in mitochondrial DNA (mtDNA) in the liver and skeletal muscle of SCNT fetuses at day 80 of gestation, with no significant decrease observed in the brain. The depletion of mtDNA is associated with hepatomegaly and muscle hypertrophy of SCNT fetuses, indicating that it is a major signature of perturbations after SCNT. The expression of selected nuclear-encoded genes pivotal for mtDNA replication is similar to controls, suggesting that the mitochondrial perturbation in interaction with incomplete nuclear reprogramming drives abnormal epigenetic features and correlated phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jiajun Zhu, Simon Schworer, Mirela Berisa, Yeon Ju Kyung, Keun Woo Ryu, Junmei Yi, Xuejun Jiang, Justin R. Cross, Craig B. Thompson
Summary: NADK2 is crucial for mitochondrial NADP(H) generation, which is essential for cell proliferation and proline biosynthesis. Its deletion can impact cell growth.
Article
Biology
David Molina-Granada, Emiliano Gonzalez-Vioque, Marris G. Dibley, Raquel Cabrera-Perez, Antoni Vallbona-Garcia, Javier Torres-Torronteras, Leonid A. Sazanov, Michael T. Ryan, Yolanda Camara, Ramon Marti
Summary: Imbalanced mitochondrial dNTP pools play a crucial role in the pathogenesis of various human diseases. This study reveals that dGTP is overrepresented among other dNTPs in mitochondria and is mainly bound to NDUFA10, an accessory subunit of complex I of the mitochondrial respiratory chain. Mutations in the dNK domain of NDUFA10 lead to reduced dGTP binding capacity and decrease mitochondrial dGTP content, suggesting a potential mechanism linking mitochondrial dNTP availability and oxidative metabolism.
COMMUNICATIONS BIOLOGY
(2022)
Article
Clinical Neurology
Cansu Altuntas, Tugce Aksu Uzunhan, Biray Erturk, Mey Talip Petmezci, Nafiye Emel Cakar, Bilge Noyan, Ali Ihsan Dokucu, Hasan Onal
Summary: MNGIE is a well-known mitochondrial depletion syndrome linked to POLG1 mutations. We present a case of a female patient with early onset disease and leukoencephalopathy compatible with classic MNGIE, who was found to have homozygous POLG1 mutation compatible with MNGIE-like syndrome, mitochondrial depletion syndrome type 4b.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2023)
Article
Cell Biology
Jun Cao, Sunil K. Verma, Elizabeth Jaworski, Stephanie Mohan, Chloe K. Nagasawa, Kempaiah Rayavara, Amanda Sooter, Sierra N. Miller, Richard J. Holcomb, Mason J. Powell, Ping Ji, Nathan D. Elrod, Eda Yildirim, Eric J. Wagner, Vsevolod Popov, Nisha J. Garg, Andrew L. Routh, Muge N. Kuyumcu-Martinez
Summary: The study uncovered a role for RBFOX2 in maintaining alternative polyadenylation signatures in myoblasts, influencing the mRNA levels and isoform expression of various genes, including those related to mitochondria and muscle contraction. Depletion of RBFOX2 negatively impacted mitochondrial health in myoblasts, particularly through disruption of APA in the Slc25a4 gene.
Article
Biochemical Research Methods
Caleb A. Lareau, Vincent Liu, Christoph Muus, Samantha D. Praktiknjo, Lena Nitsch, Pauline Kautz, Katalin Sandor, Yajie Yin, Jacob C. Gutierrez, Karin Pelka, Ansuman T. Satpathy, Aviv Regev, Vijay G. Sankaran, Leif S. Ludwig
Summary: The study developed a single-cell multi-omic approach called 'mtscATAC-seq' that enables simultaneous genotyping of mitochondrial DNA and profiling of accessible chromatin. By leveraging somatic mtDNA mutations, this method allows inference of clonal relationships among ex vivo-derived human cells. This technique provides a broadly applicable platform to map clonal relationships between cells in human tissues and enable additional modes of multi-omic discovery.
Article
Biochemistry & Molecular Biology
Sung-Ik Cho, Seonghyun Lee, Young Geun Mok, Kayeong Lim, Jaesuk Lee, Ji Min Lee, Eugene Chung, Jin-Soo Kim
Summary: Mitochondrial DNA editing is crucial for modeling mitochondrial genetic disorders and potential future treatments. This study presents a new editing enzyme called TALEDs, which efficiently induce A-to-G editing in human mitochondria.
Article
Gastroenterology & Hepatology
Dimitri Loureiro, Issam Tout, Stephanie Narguet, Cheikh Mohamed Bed, Morgane Roinard, Ahmad Sleiman, Nathalie Boyer, Nathalie Pons-Kerjean, Corinne Castelnau, Nathalie Giuly, Dorothy Tonui, Vassili Soumelis, Jamel El Benna, Patrick Soussan, Richard Moreau, Valerie Paradis, Abdellah Mansouri, Tarik Asselah
Summary: This study found that hepatitis B virus (HBV) infection can alter liver mitochondria and lead to changes in mitochondrial function and DNA damage associated with cirrhosis and fibrosis. In vitro experiments showed that HBV replication or expression of HBV X protein can induce the production of reactive oxygen species and nitric oxide, as well as mitochondrial DNA damage and impairment of mitochondrial function. These findings suggest that mitochondria may be a new target for drug development to prevent fibrosis progression.
Article
Multidisciplinary Sciences
Wouter A. van der Heijden, Lisa van de Wijer, Martin Jaeger, Karin Grintjes, Mihai G. Netea, Rolf T. Urbanus, Reinout van Crevel, Lambertus P. van den Heuvel, Maaike Brink, Richard J. Rodenburg, Philip G. de Groot, Andre J. van der Ven, Quirijn de Mast
Summary: HIV infection and antiretroviral therapy are associated with mitochondrial dysfunction in platelets. Platelet mitochondrial DNA content and function are lower in people living with HIV, leading to platelet dysfunction and increased risk of inflammatory diseases. Targeted interventions to preserve normal platelet mitochondrial function may be beneficial for individuals with HIV.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Michele Brischigliaro, Massimo Zeviani
Summary: COX deficiency is characterized by genetic and phenotypic heterogeneity, affecting the whole organism or specific tissues with different disease onsets. Over 30 genes have been linked to COX deficiency, and research on the enzyme's functional features and phenotypical consequences continues to expand through experimental models.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Biochemistry & Molecular Biology
Erika Fernandez-Vizarra, Massimo Zeviani
Summary: Mitochondrial disorders are common inborn errors of metabolism, primarily due to dysfunction of the oxidative phosphorylation system (OXPHOS). Around half of diagnosed cases have a known genetic cause, often involving pathogenic variants in genes encoding structural subunits or factors directly involved in ETC assembly.
Review
Biochemistry & Molecular Biology
Margherita Protasoni, Massimo Zeviani
Summary: Mitochondria are intracellular organelles responsible for energy production in eukaryotic cells, with growing interest due to their association with various pathologies. Dysfunction of mitochondria can lead to a wide range of clinical phenotypes, particularly affecting tissues with high-energy demand. Mitochondrial diseases are genetically heterogeneous conditions, making it difficult to identify common causes and potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Erika Fernandez-Vizarra, Sandra Lopez-Calcerrada, Luke E. Formosa, Rafael Perez-Perez, Shujing Ding, Ian M. Fearnley, Joaquin Arenas, Miguel A. Martin, Massimo Zeviani, Michael T. Ryan, Cristina Ugalde
Summary: The study of mitochondrial respiratory chain function in relation to its structural organization is essential for understanding eukaryotic cell metabolism. The complexome profiling technique has provided valuable information on the composition and assembly of MRC complexes, including larger supercomplexes and respirasomes. SCAFI plays a role in connecting individual MRC complexes III and IV, but is not the main player in respirasome formation as previously thought.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Cell Biology
Kristyna Cunatova, David Pajuelo Reguera, Marek Vrbacky, Erika Fernandez-Vizarra, Shujing Ding, Ian M. Fearnley, Massimo Zeviani, Josef Houstek, Tomas Mracek, Petr Pecina
Summary: The study reveals that in the OXPHOS system localized in the inner mitochondrial membrane, interconnected complexes form supercomplexes to maintain ATP production. Deficiencies in cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) affect the formation and maintenance of NADH dehydrogenase (cI). Experimental evidence confirms the interdependency between cI and cIV.
Article
Biochemistry & Molecular Biology
Pedro Silva-Pinheiro, Carlos Pardo-Hernandez, Aurelio Reyes, Lisa Tilokani, Anup Mishra, Raffaele Cerutti, Shuaifeng Li, Dieu-Hien Rozsivalova, Sebastian Valenzuela, Sukru A. Dogan, Bradley Peter, Patricio Fernandez-Silva, Aleksandra Trifunovic, Julien Prudent, Michal Minczuk, Laurence Bindoff, Bertil Macao, Massimo Zeviani, Maria Falkenberg, Carlo Viscomi
Summary: Mutations in the POLG gene cause a range of disorders characterized by mtDNA instability. Researchers generated a mouse model with the A449T mutation, which impairs POL gamma activity and leads to reduced levels of POL gamma A, suggesting a potential target for future therapies.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Pediatrics
Vasantha Lakshmi Gowda, Miguel Fernandez, Manish Prasad, Anne-Marie Childs, Imelda Hughes, Sandya Tirupathi, Christian Gaudentius Engelbert Lourens De Goede, Declan O'Rourke, Deepak Parasuraman, Tracey Willis, Samira Saberian, Ian Davidson
Summary: The research describes the pre-diagnosis pathway of Duchenne Muscular Dystrophy patients at key stages and identifies opportunities for service improvement. The majority of the data mirrored the benchmark audit, but there was a presentational delay observed, indicating a lack of early symptom recognition as a contributing factor.
ARCHIVES OF DISEASE IN CHILDHOOD
(2022)
Review
Biochemistry & Molecular Biology
Massimo Zeviani, Valerio Carelli
Summary: The retina is a vulnerable target for defects in oxidative phosphorylation (OXPHOS) due to mitochondrial impairment, resulting in conditions such as retinal dystrophy and optic atrophy. Mutations in mitochondrial DNA (mtDNA) and nuclear genes are implicated in mitochondrial retinopathies, presenting as isolated diseases or part of more complex syndromes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Federica Trucco, Deborah Ridout, Joana Domingos, Kate Maresh, Mary Chesshyre, Pinki Munot, Anna Sarkozy, Stephanie Robb, Rosaline Quinlivan, Mollie Riley, Colin Wallis, Elaine Chan, Francois Abel, Silvana De Lucia, Jean-Yves Hogrel, Erik H. Niks, Imelda de Groot, Laurent Servais, Volker Straub, Valeria Ricotti, Adnan Manzur, Francesco Muntoni
Summary: The study investigated the respiratory progression in four DMD genotypes relevant in ongoing exon-skipping therapeutic strategies. Results showed that different genotypes have different effects on respiratory function, which is valuable for prognosis and evaluation of treatment options.
Article
Genetics & Heredity
Georgia Stimpson, Sarah Raquq, Mary Chesshyre, Mary Fewtrell, Deborah Ridout, Anna Sarkozy, Adnan Manzur, Vandana Ayyar Gupta, Ramona De Amicis, Francesco Muntoni, Giovanni Baranello
Summary: The objective of this study was to analyze growth data (weight, height, and BMI) in ambulatory boys aged 5-12 years with Duchenne muscular dystrophy (DMD) using retrospective, observational, longitudinal data. The study considered glucocorticoids use, dystrophin isoforms, amenability to exon skipping drug subgroups, and the impact of growth on loss of ambulation. The results showed that boys in the daily regime subgroups had slower yearly height growth compared to those who were not treated. Boys with affected expression of certain dystrophin isoforms were shorter than those with unaffected expression. Increased weight was not associated with earlier loss of ambulation, but taller boys at the age of 10-11 years were more at risk of losing ambulation.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Cell Biology
Massimo Zeviani, Carlo Viscomi
Summary: Mitochondria are vital organelles responsible for generating energy in cells. Mutations in mtDNA or nuclear genes can lead to complex neurological disorders. Understanding these diseases is essential for the field of mitochondrial medicine due to the diverse genetic and phenotypic heterogeneity.
Article
Medicine, General & Internal
Jean K. Mah, Paula R. Clemens, Michela Guglieri, Edward C. Smith, Richard S. Finkel, Mar Tulinius, Yoram Nevo, Monique M. Ryan, Richard Webster, Diana Castro, Nancy L. Kuntz, Craig M. McDonald, Jesse M. Damsker, Benjamin D. Schwartz, Laurel J. Mengle-Gaw, Stefan Jackowski, Georgia Stimpson, Deborah A. Ridout, Vandana Ayyar-Gupta, Giovanni Baranello, Adnan Y. Manzur, Francesco Muntoni, Heather Gordish-Dressman, Mika Leinonen, Leanne M. Ward, Eric P. Hoffman, Utkarsh J. Dang
Summary: This study found that vamorolone treatment did not lead to changes in TTSTAND velocity among boys with DMD aged 4 to 7 years after 30 months. Vamorolone showed maintenance of muscle strength and function, similar to glucocorticoid therapy, and improved height velocity compared to glucocorticoid treatment.
Meeting Abstract
Clinical Neurology
Vasantha Gowda, Elizabeth Wraige, Min Ong, Mark Atherton, Anirban Majumdar, Silvia Sanchez Marco, Imelda Hughes, Gary Mccullagh, Francesco Muntoni, Heinz Jungbluth
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Review
Pediatrics
Vasantha Lakshmi Gowda, Miguel A. Fernandez-Garcia, Heinz Jungbluth, Elizabeth Wraige
Summary: Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by gene mutations. Clinical trials have shown that several compounds can restore survival motor neuron (SMN) protein production in SMA patients, thus altering the natural course of the disease. Currently, three drugs have been authorized for SMA treatment. However, clinicians face challenges in using these drugs, and early diagnosis at the pre-symptomatic stage is crucial.
ARCHIVES OF DISEASE IN CHILDHOOD
(2023)
Article
Pediatrics
Vasantha Lakshmi Gowda, Heinz Jungbluth, Elizabeth Wraige
ARCHIVES OF DISEASE IN CHILDHOOD-EDUCATION AND PRACTICE EDITION
(2023)