Review
Genetics & Heredity
Danyang Li, Chunmei Liang, Tao Zhang, Jordan Lee Marley, Weiwei Zou, Muqing Lian, Dongmei Ji
Summary: This review elaborates on the characteristics of the m.3243A > G mutation, from genetics to phenotype and the relationship between them, as well as potential strategies for disease prevention, providing guidance for clinicians providing genetic counseling to m.3243A > G patients.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Sara Illodo, Cibran Perez-Gonzalez, Ramiro Barcia, Flor Rodriguez-Prieto, Wajih Al-Soufi, Mercedes Novo
Summary: Guanine quadruplexes (G4s) are four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of G4 structures within mitochondrial DNA has brought significant advancements to the field. This study investigates the relevant G4 structures formed within CSB II and reveals the stability differences among different sequences.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Analytical
Ming-Hao Hu
Summary: This study successfully designed a near-infrared fluorescence probe IZIN-1 through engineering, which can track the formation of mtDNA G4 in live cells. This provides a promising example of designing a fluorescent probe targeting mtDNA G4, and offers a feasible chemical tool for investigating mtDNA G4s in live cells.
ANALYTICA CHIMICA ACTA
(2021)
Article
Chemistry, Analytical
Lijuan Yin, Ninghui Duan, Si Chen, Yuan Yao, Jifeng Liu, Long Ma
Summary: A G-quadruplex-based CRISPR-Cas12a bioassay was developed for high sensitivity and visualization detection of Salmonella. The method achieved a detection limit of 1 CFU/mL for Salmonella and successfully detected the bacteria in real food samples.
SENSORS AND ACTUATORS B-CHEMICAL
(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
Chemistry, Multidisciplinary
Anup Pandith, Yongyang Luo, Yul Jang, Jeehyeon Bae, Youngmi Kim
Summary: In this study, a fluorogenic probe CV2 was developed for the selective monitoring of G-quadruplex (G4) structures in living cells. CV2 specifically recognizes parallel G4 DNA and forms self-assembled nanoaggregates with red excimer-emitting fluorescence. The specific binding of CV2 to G4s triggers its disassembly into monomeric dyes, leading to a significant fluorescence enhancement. Moreover, CV2 can selectively stain G4s in mitochondria, making it useful for investigating the potential roles of mitochondrial DNA G4s in diseases involving mitochondrial dysfunction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Uwe Richter, Robert McFarland, Robert W. Taylor, Sarah J. Pickett
Summary: Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders caused by pathogenic variants in either the nuclear or mitochondrial genome. This review focuses on the most common pathogenic mt-tRNA variants, exploring their clinical manifestations, molecular pathologies, and potential molecular mechanisms of disease. Additionally, the role of mitochondrial-nuclear crosstalk in the manifestation of mt-tRNA-associated disease and the potential for developing treatment options are discussed.
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.
Article
Endocrinology & Metabolism
Atsuko Imai-Okazaki, Kazuhiro R. Nitta, Yukiko Yatsuka, Ayumu Sugiura, Masato Arao, Masaru Shimura, Tomohiro Ebihara, Takanori Onuki, Keiko Ichimoto, Akira Ohtake, Kei Murayama, Yasushi Okazaki
Summary: This study investigated the distribution of pathogenic mitochondrial DNA heteroplasmy at the single-cell level in skin fibroblasts from individuals with the m.3243A>G variant. Different distribution patterns were found among individuals with similar averaged heteroplasmy rates and normal mitochondrial respiratory chain enzyme activity. Further studies are needed to determine if these different distribution patterns explain the different clinical outcomes.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Engineering, Environmental
Yakun Wang, Niping Chen, Zhenxing Pan, Zhaoyi Ye, Jiongpeng Yuan, Yaoxun Zeng, Wei Long, Wangqing Bian, Xiaojing Li, Kun Zhang, Yan He, Xujie Liu
Summary: This study presents the design and synthesis of a fluorescent probe SPN for detecting and stabilizing mtDNA G4s. The results show that SPN has a high sensitivity with a low detection limit and can effectively monitor G4s in cancer cells, indicating its potential applications in cancer diagnosis.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Spectroscopy
Yongqiang Kang, Chunying Wei
Summary: This study investigates the interaction and cellular distribution of two novel stilbene derivatives with G-quadruplex DNA. The compounds exhibit low cytotoxicity and higher affinity towards G-quadruplex DNA compared to other secondary structures. The results show that 2b has a stronger affinity to G-quadruplex DNA than 2a. Additionally, the compounds not only stabilize the G-quadruplex structure but also induce the folding of G-rich sequences into a mixed-type G-quadruplex. Moreover, 2b is found to be a potential dual-channel fluorescent probe for mitochondrial G-quadruplex DNA in living cells.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Pharmacology & Pharmacy
Qiong Huang, Xiao Wang, An Chen, Hua Zhang, Qimeng Yu, Chenfeng Shen, Annoor Awadasseid, Xiaoyin Zhao, Xuqiong Xiong, Yanling Wu, Wen Zhang
Summary: A series of new naphthalimide derivatives have been designed and synthesized, among which compound 7c displayed the strongest anti-tumor activity with the best selectivity for HepG2 cells. It was found that 7c induced HepG2 cell apoptosis, hindered cancer cell migration, and arrested the cell cycle at the G2/M phase. Mechanism studies revealed that 7c selectively induced a G-rich HRCC DNA sequence in the mitochondria to form a G-quadruplex structure, causing mitochondrial dysfunction and ultimately leading to proliferative inhibition and apoptosis of cancer cells.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Pei - Tsai, Ekaterina Korotkevich, Patrick H. O'Farrell
Summary: Unknown processes lead to accumulation of mitochondrial DNA mutations, which promote heteroplasmic mitochondrial diseases and degenerative changes with aging. Purifying selection operates during development and growth, but loses effectiveness during aging. Quality control pathways and pharmacological interventions can mitigate accumulation of deleterious mutations and improve health span.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Sanna Ryytty, Riikka H. Hamalainen
Summary: The m.3243A>G mutation in the MT-TL1 gene is a common point mutation in human mtDNA, with varying symptoms and severity. The reasons for the heterogeneity and limited treatment options are unknown. Cell models, such as patient-derived and cybrid models, have provided insights into the cell-type-specific effects and tolerance of this mutation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Larry N. Singh, Brian Ennis, Bryn Loneragan, Noah L. Tsao, M. Isabel G. Lopez Sanchez, Jianping Li, Patrick Acheampong, Oanh Tran, Ian A. Trounce, Yuankun Zhu, Prasanth Potluri, Beverly S. Emanuel, Daniel J. Rader, Zoltan Arany, Scott M. Damrauer, Adam C. Resnick, Stewart A. Anderson, Douglas C. Wallace
Summary: The study introduces a novel software, MitoScape, which accurately extracts mitochondrial DNA sequences using machine learning to model the unique characteristics of mitochondrial genetics, showing superior performance in heteroplasmy estimation. By applying MitoScape to common disease examples, important heteroplasmy-disease associations are discovered, highlighting its importance in personalized medicine and clinical diagnostics.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Ophthalmology
Kit Green Sanderson, Eoghan Millar, Anupreet Tumber, Regan Klatt, Neal Sondheimer, Ajoy Vincent
Summary: This is the first documented case of an electronegative ERG in a POLG-related disorder, demonstrating wide phenotypic overlap. The patient exhibited systemic symptoms in addition to ophthalmological features and carried a homozygous mutation in POLG.
DOCUMENTA OPHTHALMOLOGICA
(2021)
Article
Genetics & Heredity
Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson, Devon Knight, Sonal Mahida, Donnice Michel, Mark Tarnopolsky, Annapurna Poduri, Alexander Rotenberg, Neal Sondheimer, Ralph J. DeBerardinis
Summary: This study identified a rare homozygous variant in UFSP2 gene associated with neurodevelopmental delay and epilepsy. The variant alters the UFMylation pathway and impairs de-UFMylation in patient-derived fibroblasts. Different UFSP2 variants may cause diverse clinical consequences, highlighting the importance of understanding these genetic variations.
GENETICS IN MEDICINE
(2021)
Article
Multidisciplinary Sciences
Angela Duong, Alesya Evstratova, Adam Sivitilli, J. Javier Hernandez, Jessica Gosio, Azizia Wahedi, Neal Sondheimer, Jeff L. Wrana, Jean-Martin Beaulieu, Liliana Attisano, Ana C. Andreazza
Summary: The study developed cerebral organoids (COs) from induced pluripotent stem cells (iPSCs) derived from human peripheral blood mononuclear cells (PBMCs) and monitored mitochondrial health from the primary, reprogrammed and differentiated stages. Results show preserved mitochondrial genetics, function and treatment responses throughout the process, with measurable neuronal activity in the COs.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Priyanka Nandakumar, Chao Tian, Jared O'Connell, David Hinds, Andrew D. Paterson, Neal Sondheimer
Summary: The nuclear genome plays a role in maintaining the stability of the mitochondrial genome, with mtDNA sequence variants able to exist in a state of heteroplasmy. This heteroplasmy can be influenced by age, sex, and mitochondrial haplogroup, with genome-wide association studies identifying 20 loci for heteroplasmy, including a region overlapping the mitochondrial transcription factor A (TFAM). These findings suggest that mitochondrial heteroplasmy has a heritable nuclear component.
Article
Biochemistry & Molecular Biology
Matthew A. Lines, Alexanne Cuillerier, Pranesh Chakraborty, Turaya Naas, M. Laura Duque Lasio, Jean Michaud, Chantal Pileggi, Mary-Ellen Harper, Yan Burelle, Tomi L. Toler, Neal Sondheimer, Heather P. Crawford, Francisca Millan, Michael T. Geraghty
Summary: Mitochondrial disorders are a rare group of degenerative multisystem disorders affecting core bioenergetic and signalling functions of cells. This study identified a novel neonatal-onset mitochondriopathy in three infants, characterized by failure to thrive, high lactate and ammonia levels. Exome sequencing revealed a recurrent de novo substitution in ATP5F1A, leading to deficits in complex V function and expression in patient-derived fibroblasts. The long-term prognosis of this disorder, which presents with life-threatening neonatal manifestations, remains unclear.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Grzegorz L. Ciesielski, Shalom Kim, Carolina de Bovi Pontes, Laurie S. Kaguni
Summary: This study reveals a direct interaction between mitochondrial single-stranded DNA-binding protein (mtSSB) and the catalytic subunit of mitochondrial replicative DNA polymerase, Pol gamma alpha, impacting DNA synthesis and exonucleolysis. The balance between attractive and repulsive affinities in the interaction between mtSSB and polymerase gamma holoenzyme (Pol gamma) plays a key role in these processes.
FRONTIERS IN GENETICS
(2021)
Review
Health Care Sciences & Services
Sara Rotenberg, Danae Rodriguez Gatta, Azizia Wahedi, Rachelle Loo, Emily McFadden, Sara Ryan
Summary: This study aimed to understand the literature on training health workers about disability, finding that training involving people with disabilities was most effective, including community placements, simulations, and interactive sessions. It is recommended that health workers worldwide receive comprehensive training to improve the health outcomes of people with disabilities.
DISABILITY AND HEALTH JOURNAL
(2022)
Article
Genetics & Heredity
Minyoung So, Johnny Stiban, Grzegorz L. Ciesielski, Stacy L. Hovde, Laurie S. Kaguni
Summary: Recent evidence indicates that iron-sulfur clusters in DNA replicative proteins sense DNA-mediated charge transfer to regulate nuclear DNA replication. The presence of an ISC and a metal cofactor in the Dm mtDNA helicase was confirmed, with the NTD also playing a role in membrane binding. The NTD binds to liposomes mimicking phospholipid membranes through electrostatic interactions, with a higher specificity as cardiolipin content increases.
FRONTIERS IN GENETICS
(2021)
Meeting Abstract
Biochemistry & Molecular Biology
Carolina de Bovi Pontes, Cody Jefferys, Muhamad Bedwan, Elena J. Ciesielska, Grzegorz L. Ciesielski
Meeting Abstract
Biochemistry & Molecular Biology
Hyacintha-Ghislaine M. Bisimwa, Elena J. Ciesielska, Noelle Kim, Marcos T. Oliveira, Grzegorz L. Ciesielski
Review
Biochemistry & Molecular Biology
Ana P. C. Rodrigues, Audrey C. Novaes, Grzegorz L. Ciesielski, Marcos T. Oliveira
Summary: Drosophila is a useful model for studying mtDNA maintenance and human mtDNA diseases, as it shares similarities with mammals in terms of mtDNA-encoded genes. However, there are key differences between Drosophila and mammals in the processes of mtDNA maintenance. This review highlights the need for further research in understanding mtDNA maintenance in Drosophila and suggests potential roles for various proteins in this process.
BIOSCIENCE REPORTS
(2022)
Article
Endocrinology & Metabolism
Azizia Wahedi, Chandika Soondram, Alan E. Murphy, Nathan Skene, Shamima Rahman
Summary: Leigh syndrome is a rare and inherited neurometabolic disorder with genetic and clinical heterogeneity. The cellular specificity of genes associated with Leigh syndrome within the brain was determined using co-expression network analyses. Potential genetic commonalities between Leigh syndrome and other disorders with similar clinical features were also investigated.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Ismael Plaza-G.A., Kateryna M. Lemishko, Rodrigo Crespo, Thinh Q. Truong, Laurie S. Kaguni, Francisco J. Cao-Garcia, Grzegorz L. Ciesielski, Borja Ibarra
Summary: In this study, the molecular mechanism of strand displacement DNA synthesis by human mitochondrial DNA polymerase Pol gamma and its modulation by single-stranded DNA binding proteins (SSBs) were elucidated using single-molecule optical tweezers and biochemical assays. The results showed that SSBs stimulate Pol gamma's strand displacement activity through multiple mechanisms, playing a significant role in the replication of human mitochondrial DNA.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Clinical Neurology
Ghalia Al Yazidi, Jaap Mulder, Christoph Licht, Elizabeth Harvey, James Robertson, Neal Sondheimer, Ingrid Tein
Summary: Patients with MELAS syndrome can have rapid recovery with high dose IV L-Arg treatment and can maintain higher serum arginine concentrations and better tolerance with oral L-Arg maintenance therapy. Maintenance therapy can reduce SLEs and seizures.