Article
Genetics & Heredity
Maria J. Nabais Sa, Kerry A. Miller, Mary McQuaid, Nils Koelling, Andrew O. M. Wilkie, Hugo Wurtele, Arjan P. M. de Brouwer, Jorge Oliveira
Summary: The study identified a novel disease-associated gene GINS2 in Meier-Gorlin syndrome (MGORS), expanding the genetic etiology of the disorder. A novel homozygous missense variant in GINS2 was identified through exome sequencing, leading to increased sensitivity to nicotinamide and potential disruption of the effective interaction between the GINS complex and CDC45.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Obstetrics & Gynecology
Xing-Yu Zhou, Yi-Zhen Yang, Jun Zhang, Xiao-Fei Zhang, Yu-Dong Liu, Zhe Wang, Shi-Ling Chen
Summary: This study assessed the levels of cell-free mitochondrial DNA (cf-mtDNA) in plasma and follicular fluid (FF) of premature ovarian insufficiency (POI) patients and investigated its potential role in predicting disease progression and pregnancy outcomes.
BMC PREGNANCY AND CHILDBIRTH
(2023)
Article
Biochemistry & Molecular Biology
Kimberly K. Richardson, Wen Ling, Kimberly Krager, Qiang Fu, Stephanie D. Byrum, Rupak Pathak, Nukhet Aykin-Burns, Ha-Neui Kim
Summary: This study found that exposure to multiple fractions of low-dose radiation or a single exposure to the same total dose of radiation can cause a decrease in trabecular bone mass in male mice. The damaging effect is associated with highly activated bone resorption and increased expression and activity of Sirt3, a protein essential for osteoclast mitochondrial activity. Osteoclast progenitors lacking Sirt3 exhibit impaired resorptive activity when exposed to radiation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Xiaohua Xu, Chou-Wei Chang, Min Li, Chao Liu, Yilun Liu
Summary: The RECQ4 gene encodes an ATP-dependent DNA helicase in human cells, mutations of which are linked to various clinical diseases and high cancer risks. Understanding the molecular dysfunctions of different RECQ4 disease mutations is crucial for improving our knowledge of RECQ4 clinical phenotypes and its roles in cancer development.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Reproductive Biology
Zhixian Zhou, Huan Yin, Suye Suye, Zhen Ren, Lei Yan, Liye Shi, Chun Fu
Summary: Fance defects inhibit the mitotic proliferation of primordial germ cells, leading to decreased numbers and abnormal cell cycle distribution.
JOURNAL OF OVARIAN RESEARCH
(2023)
Article
Cell Biology
Ayuka Ehara, Daisuke Taguchi, Kazuhiko Nakadate, Shuichi Ueda
Summary: Atrn has been found to be expressed in both slow-twitch and fast-twitch muscles, with mAtrn mainly expressed in slow-twitch muscles. Atrn deficiency may lead to reduced expression of antioxidant enzymes and mitochondrial functional proteins, resulting in morphological abnormalities in muscles.
CELL AND TISSUE RESEARCH
(2021)
Article
Evolutionary Biology
Ryo Harada, Yuji Inagaki
Summary: The study suggests that mitochondrion-localized DNA polymerases likely originated from a single DNA polymerase, possibly obtained horizontally from phages. This indicates a potentially significant contribution of proteins acquired via nonvertical processes to the machinery for mtDNA maintenance in kinetoplastids and diplonemids.
GENOME BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Ke Zhang, Yang Sui, Wu-Long Li, Gen Chen, Xue-Chang Wu, Robert J. Kokoska, Thomas D. Petes, Dao-Qiong Zheng
Summary: The deficiency of Pol epsilon leads to genomic instability and multiple human diseases. Low levels of Pol epsilon result in cellular changes such as elevated rates of recombination, aneuploidy, contraction of ribosomal DNA repeats, shortened telomeres, increased break-induced replication, and higher rate of single-base mutations. Compared to other replicative DNA polymerases, Pol epsilon displays distinct patterns of genomic alterations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Biochemistry & Molecular Biology
Ilona Faustova, Mart Loog
Summary: Study by Hossain et al. (2021) reveals that ORC1 and CDC6 interact during pre-replicative complex formation in G1, mediated by SLiMs in IDRs and regulated by CDKs.
Article
Genetics & Heredity
Hemanth Tummala, Amanda Walne, Roberto Buccafusca, Jenna Alnajar, Anita Szabo, Peter Robinson, Allyn McConkie-Rosell, Meredith Wilson, Suzanne Crowley, Veronica Kinsler, Anna-Maria Ewins, Pradeepa M. Madapura, Manthan Patel, Nikolas Pontikos, Veryan Codd, Tom Vulliamy, Inderjeet Dokal
Summary: Dyskeratosis congenita (DC) is a genetic bone-marrow-failure disorder characterized by abnormal skin pigmentation, nail dystrophy, and oral leucoplakia. A study identified heterozygous germline variants in the TYMS gene as the cause of DC in eight affected families. The variants resulted in TYMS deficiency, altered nucleotide metabolism, and genotoxic stress.
AMERICAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Dongyang Xu, Lingcong Luo, Yu Huang, Meng Lu, Lu Tang, Yong Diao, Philipp Kapranov
Summary: This study established a high-throughput method based on next-generation sequencing to identify replication start sites of mitochondrial genomes at nucleotide-level resolution. The results revealed complex and highly reproducible patterns of mitochondrial initiation sites, indicating the dynamic nature of replication initiation in different cell types and species. Overall, this work highlights the gaps in our understanding of mitochondrial DNA replication and provides a new avenue for further research on mitochondrial and potentially other genomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Joon Park, Noe Baruch-Torres, Y. Whitney Yin
Summary: Human mitochondrial DNA (mtDNA) is a circular double-stranded DNA, responsible for encoding subunits of the electron transfer chain and essential RNAs for mitochondrial protein translation. The minimal mtDNA replisome consists of Twinkle, DNA polymerase gamma, and mitochondrial single-stranded DNA-binding protein. Both mitochondrial RNA transcription and DNA replication machineries are intertwined and regulate mtDNA copy numbers, cellular energy supplies, and cellular metabolism. This review focuses on the structural aspects of the mechanisms governing these pathways, and the mtDNA diseases caused by mutations in transcription and replication machineries. Additionally, it discusses the adverse effects of antiviral drugs on mitochondrial DNA and RNA polymerases, as well as potential structural approaches for developing less toxic nucleoside reverse transcriptase inhibitors and ribonucleoside analogs.
Review
Biochemistry & Molecular Biology
Yanduo Zhang, Kailong Hou, Jinkai Tong, Haonan Zhang, Mengjie Xiong, Jing Liu, Shuting Jia
Summary: This review provides a comprehensive overview of the current findings on the regulation of ALT by Shelterin components, aiming to enhance the understanding of altered functions of Shelterin components in ALT cells and to identify potential targets for the treatment of ALT tumor cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Ethiraj Ravindran, Cynthia Gutierrez de Velazco, Ali Ghazanfar, Nadine Kraemer, Sami Zaqout, Abdul Waheed, Mohsan Hanif, Sadia Mughal, Alessandro Prigione, Na Li, Xiang Fang, Hao Hu, Angela M. Kaindl
Summary: Mutations in MCM7 are identified as a novel cause of autosomal recessive primary microcephaly (MCPH) and intellectual disability, highlighting its crucial role in nervous system development. The expression pattern of MCM7 is consistent in mouse and human cells, affecting cell viability and proliferation.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Cell Biology
Wan-Ping Bian, Shi-Ya Pu, Shao-Lin Xie, Chao Wang, Shun Deng, Phyllis R. Strauss, De-Sheng Pei
Summary: In this study, a new mutant with mpv17 knockout was developed using the CRISPR/Cas9 system. The mpv17(-/-) zebrafish exhibited developmental defects in muscles, liver, and energy supply, likely due to severe mitochondria dysfunction. The introduction of normal exogenous mitochondria through microinjection partially restored the expression of genes involved in TAG metabolism.
CELL DEATH DISCOVERY
(2021)
Review
Genetics & Heredity
Juan Luque, Ingrid Mendes, Beatriz Gomez, Beatriz Morte, Miguel Lopez de Heredia, Enrique Herreras, Virginia Corrochano, Juan Bueren, Pia Gallano, Rafael Artuch, Cristina Fillat, Luis A. Perez-Jurado, Lluis Montoliu, Angel Carracedo, Jose M. Millan, Susan M. Webb, Francesc Palau, Pablo Lapunzina
Summary: CIBERER, a thematic area of CIBER, focuses on rare disease research. It aims to facilitate collaboration between biomedical and clinical research groups and provide new tools for the diagnosis and therapy of low-prevalence diseases.
Article
Biology
Manuel Spitschan, Nayantara Santhi, Amrita Ahluwalia, Dorothee Fischer, Lilian Hunt, Natasha A. Karp, Francis Levi, Ines Pineda-Torra, Parisa Vidafar, Rhiannon White
Summary: Growing evidence suggests that sex differences have a significant impact on various aspects of human biology. This review focuses on exploring the influence of sex on the circadian and sleep physiology of humans and identifies a data gap in investigating the non-visual effects of light. A virtual workshop on the biomedical implications of sex differences in sleep and circadian physiology highlights the need for inclusive and accessible research design, recruitment strategies to achieve a balanced sample size, utilization of data visualization to understand the influence of sex, statistical analyses that incorporate sex as a factor, and making participant-level data open for future meta-analytic efforts.
Article
Pathology
Gemma Bullich, Leslie Matalonga, Montserrat Pujadas, Anastasios Papakonstantinou, Davide Piscia, Rafael Artuch, Pia Gallano, Gloria Garrabou, Juan R. Gonzalez, Daniel Grinberg, Miriam Guitart, Steven Laurie, Conxi Lazaro, Cristina Luengo, Ramon Marti, Montserrat Mila, David Ovelleiro, Genis Parra, Aurora Pujol, Eduardo Tizzano, Alfons Macaya, Francesc Palau, Antonia Ribes, Luis A. Perez-Jurado, Sergi Beltran
Summary: Many rare disease patients remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield. The Undiagnosed Rare Disease Program of Catalonia project reanalyzed genomic data from 323 families with a neurologic rare disease, leading to a diagnosis for 20.7% of the patients.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Editorial Material
Clinical Neurology
Carlos Lopez-Gomez, Yolanda Camara, Michio Hirano, Ramon Marti
NEUROMUSCULAR DISORDERS
(2022)
Article
Multidisciplinary Sciences
Thomas D. Jackson, Jordan J. Crameri, Linden Muellner-Wong, Ann E. Frazier, Catherine S. Palmer, Luke E. Formosa, Daniella H. Hock, Kenji M. Fujihara, Tegan Stait, Alice J. Sharpe, David R. Thorburn, Michael T. Ryan, David A. Stroud, Diana Stojanovski
Summary: Sideroflexins (SFXNs) are a family of proteins that have different functions in mitochondrial biology. Loss of SFXN4 leads to complex I assembly defect and it interacts with the core components of the mitochondrial complex I intermediate assembly complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Irati Aiestaran-Zelaia, Maria Jesus Sanchez-Guisado, Marina Villar-Fernandez, Mikel Azkargorta, Lucia Fadon-Padilla, Uxoa Fernandez-Pelayo, Diego Perez-Rodriguez, Pedro Ramos-Cabrer, Antonella Spinazzola, Felix Elortza, Jesus Ruiz-Cabello, Ian J. Holt
Summary: 2-Deoxy-D-glucose (2DG) inhibits glycolysis, stimulates respiration, and restricts viral replication in cultured cells. In the murine heart, 2DG increases the respiratory chain proteome of mitochondria, enhancing oxidative capacity and potentially compensating for the energy deficit caused by glycolysis inhibition.
SCIENTIFIC REPORTS
(2022)
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
Biochemistry & Molecular Biology
Cristina Jou, Andres Nascimento, Anna Codina, Julio Montoya, Ester Lopez-Gallardo, Sonia Emperador, Eduardo Ruiz-Pesini, Raquel Montero, Daniel Natera-de Benito, Carlos Ortez, Jesus Marquez, Maria Zelaya, Alfonso Gutierrez-Mata, Carmen Badosa, Laura Carrera-Garcia, Jesica Exposito-Escudero, Monica Roldan, Yolanda Camara, Ramon Marti, Isidre Ferrer, Cecilia Jimenez-Mallebrera, Rafael Artuch
Summary: Thymidine kinase (TK2) deficiency in pediatric patients leads to mitochondrial DNA depletion syndrome. This study examines the clinical, biochemical, genetic, histopathological, and ultrastructural features of a group of pediatric patients with TK2 deficiency. Muscle biopsies show ragged red fibers in all patients, with a higher prevalence in younger patients. Inflammatory infiltrates and overexpression of MHC I are observed in younger patients. Ultrastructural analysis reveals concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles as major mitochondrial alterations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Wei Wei, Katherine R. Schon, Greg Elgar, Andrea Orioli, Melanie Tanguy, Adam Giess, Marc Tischkowitz, Mark J. Caulfield, Patrick F. Chinnery
Summary: The transfer of mitochondrial DNA into the nucleus contributes to a complex landscape of nuclear-mitochondrial segments (NUMTs). Almost all individuals have multiple NUMTs, including rare ones that are present in less than 0.1% of the population. Most NUMTs inserted into the nuclear genome after humans diverged from apes. Once inserted, the sequences are no longer under mitochondrial evolutionary constraints and have different mutational signatures compared to mitochondrial DNA.
Editorial Material
Multidisciplinary Sciences
Lilian Hunt, Mathias Wullum Nielsen, Londa Schiebinger
Review
Biochemistry & Molecular Biology
Megan J. Baker, Jordan J. Crameri, David R. Thorburn, Ann E. Frazier, Diana Stojanovski
Summary: Mitochondrial diseases are a group of metabolic disorders caused by mutations in mitochondrial DNA or nuclear genes. Primary mitochondrial disease is more widely studied than secondary mitochondrial disease. Next generation sequencing techniques have helped identify many novel mitochondrial disease genes, with approximately half linked to secondary mitochondrial disease.
Article
Medicine, General & Internal
Sarah Missen, Callum Wilson, Howard Potter, Andrea L. Vincent, Rinki Murphy, Richard Roxburgh, Miriam Rodrigues, Gemma Poke, Stephen P. Robertson, David R. Thorburn, Emma Glamuzina
Summary: This study estimated the prevalence of molecularly confirmed and suspected mitochondrial disease in New Zealand in 2015 and found that mitochondrial disease is underdiagnosed in the country. This highlights the need for improved education and referral pathways for mitochondrial disease in New Zealand.
INTERNAL MEDICINE JOURNAL
(2023)
Article
Gastroenterology & Hepatology
Luis G. Alcala-Gonzalez, Anna Accarino, Ramon Marti, Daniel Sanchez-Tejerina, Arnau Llaurado, Fernando Azpiroz, Carolina Malagelada
Summary: This study aims to describe gastrointestinal motor dysfunction in MNGIE patients using advanced techniques and evaluate the relationship between motor abnormalities and symptoms. The results show that MNGIE patients have characteristic motor dysfunction in the small bowel, even in the presence of mild digestive symptoms. Early investigation is necessary.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Article
Medicine, Research & Experimental
Jonathan Shintaku, Wolfgang M. Pernice, Wafaa Eyaid, B. G. C. Jeevan, Zuben P. Brown, Marti Juanola-Falgarona, Javier Torres-Torronteras, Ewen W. Sommerville, Debby M. E. I. Hellebrekers, Emma L. Blakely, Alan Donaldson, Ingrid van de laar, Cheng-Shiun Leu, Ramon Marti, Joachim Frank, Kurenai Tanji, David A. Koolen, Richard J. Rodenburg, Patrick F. Chinnery, H. J. M. Smeets, Grainne S. Gorman, Penelope E. Bonnen, Robert W. Taylor, Michio Hirano
Summary: This article reports 5 patients from 4 families who presented with ptosis and ophthalmoplegia as well as multiple mtDNA deletions in muscle. The study identifies RRM1 deficiency as a cause of the disease and reveals the disruption of nucleotide synthesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)