Article
Biochemistry & Molecular Biology
Liguang Zhang, Jin Ma, Zhaorui Shen, Bo Wang, Qingling Jiang, Fei Ma, Yan Ju, Guangxing Duan, Quan Zhang, Xiaodong Su, Sodmergen
Summary: Increasing the copy number of mtDNA in plant cells leads to mitochondrial dysfunction and reduced growth, while keeping low levels of mtDNA can moderate nuclear-mitochondrial incompatibility. This sheds light on why plant cells have lower mtDNA levels than animal cells.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Lorenzo Rivas-Garcia, Jose Luis Quiles, Alfonso Varela-Lopez, Francesca Giampieri, Maurizio Battino, Jorg Bettmer, Maria Montes-Bayon, Juan Llopis, Cristina Sanchez-Gonzalez
Summary: The application of metallic nanoparticles as a therapeutic tool can improve the diagnosis and treatment of diseases by targeting mitochondria, affecting cellular function, and triggering autophagy processes. Nanoparticles have the potential to be used as therapeutic agents for cancer and other diseases dependent on mitochondria.
Article
Multidisciplinary Sciences
Odei Barrenada, Eduardo Larriba, Daniel Fernandez-Perez, Miguel angel Brieno-Enriquez, Jesus del Mazo Martinez
Summary: Recent studies have shown that mitochondrial small noncoding RNAs (sncRNAs) play important roles in germ cell development and differentiation. By analyzing sequencing data, we identified the origins, expression levels, and potential functions of piRNAs, as well as their association with other sncRNAs and the mitochondrial regulatory region. Our findings suggest that mitochondria-associated piRNAs may mediate nucleo-mitochondrial communication.
SCIENTIFIC REPORTS
(2022)
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
Cell Biology
Kalliopi Chatzovoulou, Anne Mayeur, Nadine Gigarel, Fabienne Jabot-Hanin, Laetitia Hesters, Arnold Munnich, Nelly Frydman, Jean-Paul Bonnefont, Julie Steffann
Summary: Research reveals that maternal or embryonic mtDNA mutations do not affect embryonic quality or viability, and mtDNA copy number is also not altered by mtDNA mutations at this early stage.
Article
Chemistry, Multidisciplinary
Letao Yang, Christopher Rathnam, Takuya Hidaka, Yannan Hou, Brandon Conklin, Ganesh N. Pandian, Hiroshi Sugiyama, Ki-Bum Lee
Summary: The study highlights the development of a nanoparticle-based synthetic mitochondrial transcription regulator (MitoScript) for controlling mitochondrial DNA transcription. MitoScript demonstrates great colloidal stability, biocompatibility, efficient cell uptake, and selective mitochondria targeting. It effectively downregulated the expression of the ND6 gene, which impacted the cell's redox status, resulting in increased ROS generation. This technology could contribute to understanding mitochondrial disorders and developing treatments for mitochondrial diseases.
Article
Cell Biology
Raviprasad Kuthethur, Vaibhav Shukla, Sandeep Mallya, Divya Adiga, Shama Prasada Kabekkodu, Lingadakai Ramachandra, P. U. Prakash Saxena, Kapaettu Satyamoorthy, Sanjiban Chakrabarty
Summary: This study identified 13 mitochondrial genome-encoded microRNAs (mitomiRs) that are differentially expressed in breast cancer cells. The expression of mitomiRs is reduced in breast cancer cells with mitochondrial DNA depletion or inhibition of mitochondrial transcription. These mitomiRs interact with the protein Ago2 in both the cytoplasm and mitochondria and regulate the expression of nuclear and mitochondrial transcripts in breast cancer cells. This study suggests that these mitomiRs may be promising tools for expression and functional analysis in patients with mitochondrial defects.
JOURNAL OF CELL SCIENCE
(2022)
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.
Review
Medicine, Research & Experimental
Siti Muslihah Abd Radzak, Siti Zulaikha Nashwa Mohd Khair, Farizan Ahmad, Azim Patar, Zamzuri Idris, Abdul Aziz Mohamed Yusoff
Summary: Mitochondria play a critical role in cellular functions, and their quantity and composition have an impact on cellular pathways and diseases such as cancer. This review provides an overview of mtDNA copy number variations in human cancers and summarizes the existing knowledge on the regulation and machinery of mtDNA copy number.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Xingbo Yang, Jiacheng Jiang, Zongyu Li, Jiayi Liang, Yaozu Xiang
Summary: Mitochondria, as the energy powerhouse of cells, have their own unique genome separate from the nuclear genome. Mutations in mitochondrial DNA can lead to diseases and health issues, but editing these genes effectively remains a challenge. Current gene editing technologies have been explored for mitochondrial gene editing, but further research and optimization are needed for their application in this specific area.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Pharmacology & Pharmacy
Marcos R. Chiaratti, Patrick F. Chinnery
Summary: It was previously believed that humans only have one type of mitochondrial DNA (mtDNA), but recent studies have discovered that mixed populations of mtDNA are actually common. The levels of heteroplasmy, or mixed mtDNA, can change significantly during transmission and contribute to mitochondrial diseases and other late onset disorders. While initially thought to be stochastic, the segregation of mtDNA heteroplasmy is now known to be regulated by specific mechanisms. This review provides a synthesis of recent literature on the selection mechanisms for and against mtDNA variants and highlights the gaps in our understanding of this process.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Andrea Busnelli, Annalisa Navarra, Paolo Emanuele Levi-Setti
Summary: The decline in female fertility is a natural consequence of ovarian aging, with mitochondrial genome alterations playing an important role. Research focuses on the impact of mtDNA changes on female fertility and the potential use of mtDNA copy number as a biomarker. Experimental therapies, including antioxidant treatments, are being explored to combat ovarian aging.
Article
Endocrinology & Metabolism
Matthew Devall, Darren M. Soanes, Adam R. Smith, Emma L. Dempster, Rebecca G. Smith, Joe Burrage, Artemis Iatrou, Eilis Hannon, Claire Troakes, Karen Moore, Paul O'Neill, Safa Al-Sarraj, Leonard Schalkwyk, Jonathan Mill, Michael Weedon, Katie Lunnon
Summary: This study presents a novel approach to investigate the patterns of mitochondrial DNA methylation in human brain tissue. The results show relatively low but conserved patterns of mitochondrial DNA methylation, with peaks observed in the D-LOOP and several genes in a non-CpG context. Differential methylation patterns associated with age, sex, and brain region were also identified. This study provides detailed annotation of DNA methylation in the mitochondrial genome and highlights the potential role of mitochondrial epigenetic mechanisms in disorders characterized by mitochondrial dysfunction.
FRONTIERS IN ENDOCRINOLOGY
(2023)
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.
Article
Environmental Sciences
Hongjuan Wang, Huan Chen, Shulei Han, Yaning Fu, Yushan Tian, Yong Liu, An Wang, Hongwei Hou, Qingyuan Hu
Summary: The study found that nicotine addicts exhibit significantly lower mtDNA copy number in their peripheral blood compared to non-smokers, indicating detrimental effects of long-term smoking exposure on mitochondria. Nicotine also induced mitochondrial defects and reduced mtDNA levels in animal and cell models, suggesting that these effects are mediated by autophagy.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Multidisciplinary Sciences
Justin C. St John, Yogeshwar Makanji, Jacqueline L. Johnson, Te-Sha Tsai, Simone Lagondar, Fleur Rodda, Xin Sun, Mulyoto Pangestu, Penny Chen, Peter Temple-Smith
SCIENTIFIC REPORTS
(2019)
Article
Clinical Neurology
Joanna Poulton, Julie Steffann, Joerg Burgstaller, Robert McFarland, B. Arbeithuber, J. Bengoa, S. Chan, M. Chiaratti, M. Crouch, R. Dimond, J. A. Enriques, G. Gorman, L. Hyslop, I. Johnston, J. Kitto, A. Maguire, S. Mitalipov, Van Otterloo, J. Poulton, S. Sallevelt, H. Smeets, C. Spits, J. St John, J. Stewart, M. Stoneking, D. Thorburn, E. van der Veer, D. Wells
NEUROMUSCULAR DISORDERS
(2019)
Review
Cell Biology
Justin C. St John
Article
Cell Biology
Ronan Kapetanovic, Syeda Farhana Afroz, Divya Ramnath, Grace M. E. P. Lawrence, Takashi Okada, James E. B. Curson, Jost de Bruin, David P. Fairlie, Kate Schroder, Justin C. St John, Antje Blumenthal, Matthew J. Sweet
IMMUNOLOGY AND CELL BIOLOGY
(2020)
Article
Evolutionary Biology
Justin C. St John
Summary: Understanding the interactions between nuclear and mitochondrial genomes is crucial for early development and developmental progression. DNA methylation processes in the nuclear genome and changes in mitochondrial DNA copy number play key roles in establishing cellular function and metabolic status during development. Together, these actions ensure genomic balance and the establishment of the organism's life program at each developmental milestone.
ANNUAL REVIEW OF ANIMAL BIOSCIENCES, VOL 9, 2021
(2021)
Article
Genetics & Heredity
Rafiatu Azumah, Katja Hummitzsch, Monica D. Hartanti, Justin C. St. John, Richard A. Anderson, Raymond J. Rodgers
Summary: This study analyzed the expression of polycystic ovary syndrome (PCOS) candidate genes in bovine fetal ovaries and identified different expression patterns and upstream regulators associated with these genes. The early cluster of genes was mainly involved in mitochondrial function and oxidative phosphorylation, while the late cluster of genes was associated with stromal expansion, cholesterol biosynthesis, and steroidogenesis. These findings provide insights into the development and origins of PCOS, suggesting that multiple etiological pathways may contribute to the development of the syndrome.
FRONTIERS IN GENETICS
(2022)
Article
Genetics & Heredity
Takashi Okada, Stephen McIlfatrick, Nhi Hin, Nader Aryamanesh, James Breen, Justin C. St John
Summary: Mitochondrial supplementation can alter gene expression and DNA methylation patterns in pig blastocysts, potentially affecting the development of specific tissue types later in life.
EPIGENETICS & CHROMATIN
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Towarnicki, Neil A. Youngson, Susan M. Corley, Jus C. St John, Richard G. Melvin, Nigel Turner, Margaret J. Morris, J. William O. Ballard
Summary: Studies have shown that ancestral life experiences, particularly stress and diet, can influence the growth, metabolism, and behavior of future generations. This research focuses on the non-genetic inheritance between fertilization and adulthood, revealing that ancestral dietary macronutrient composition and quantity can impact the developmental timing of descendants through changes in specific signaling pathways.
Review
Biochemistry & Molecular Biology
Justin C. St John, Takashi Okada, Eryk Andreas, Alexander Penn
Summary: The mitochondrial genome resides in the mitochondria present in nearly all cell types. The porcine (Sus scrofa) mitochondrial genome is approximately 16.7 kb in size and exists in a multimeric format in cells. Different cell types have varying numbers of mitochondrial DNA (mtDNA) copy number based on their need for ATP, which is produced through oxidative phosphorylation. The oocyte, or egg cell, has the highest number of mtDNA copies among all cell types. During oogenesis, the oocyte determines the mtDNA copy number to ensure there are enough copies to support subsequent developmental events. Additionally, it initiates a program of epigenetic patterning that regulates DNA methylation levels of the nuclear genome. Once fertilized, the nuclear and mitochondrial genomes synchronize to ensure proper development of the embryo and fetus. However, altering the mtDNA copy number in the oocyte through mitochondrial supplementation can impact the programming and gene expression profiles of the developing embryo. Interestingly, oocytes that are deficient in mtDNA show improved embryo development rates and gene expression profiles. Furthermore, mtDNA haplotypes, which represent maternal origins, appear to influence developmental outcomes and certain reproductive traits. Overall, manipulating the mitochondrial content of oocytes can provide developmental advantages.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Stephen McIlfatrick, Sean O'Leary, Takashi Okada, Alexander Penn, Vy Hoang Thao Nguyen, Lisa McKenny, Shang-Yu Huang, Eryk Andreas, John Finnie, Roy Kirkwood, Justin C. St John
Summary: Introducing extra mitochondrial DNA (mtDNA) into oocytes at fertilization can rescue poor quality oocytes, but it may alter DNA methylation and gene expression profiles of preimplantation embryos. However, these alterations do not affect gross anatomical, morphological, or histopathological differences and do not lead to clinically significant lesions. The offspring of females with mtDNA supplementation exhibit modified weight and height gain, biochemical, and hematological profiles without any negative health effects.
Article
Biochemistry & Molecular Biology
Takashi Okada, Stephen McIlfatrick, Justin C. St. John
Summary: Mitochondrial DNA (mtDNA) deficiency is associated with poor oocyte quality and fertilisation failure. Supplementing mtDNA deficient oocytes with extra copies of mtDNA improves fertilisation rates and embryo development. The molecular mechanisms underlying oocyte developmental incompetence and the effects of mtDNA supplementation on embryo development are still unclear. This study investigates the association between the developmental competence of Sus scrofa oocytes, assessed with Brilliant Cresyl Blue, and transcriptome profiles. The effects of mtDNA supplementation on the developmental transition from oocyte to blastocyst are also analyzed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Takashi Okada, Alexander Penn, Justin C. C. St. John
Summary: Oocytes can be supplemented with extra copies of mtDNA to improve developmental outcome, with minor differences observed in growth and health of pigs derived from autologous and heterologous mtDNA. However, it is unclear if changes in gene expression during preimplantation development persist and affect gene expression in adult tissues, and if the source of mtDNA influences gene expression patterns. Transcriptome analyses revealed common effects on immune response and glyoxylate metabolism genes in brain, heart, and liver tissues by mtDNA supplementation, with a link to oxidative phosphorylation genes when using third-party mtDNA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Justin C. St John, Takashi Okada, Eryk Andreas, Alexander Penn
Summary: The mitochondrial genome is present in nearly all cell types and its copy number can vary in different cell types. The oocyte has the highest number of mtDNA copies and regulates its copy number to support subsequent developmental events. Manipulating the mtDNA copy number in oocytes can affect embryo development and gene expression profiles.
MOLECULAR REPRODUCTION AND DEVELOPMENT
(2023)
Article
Genetics & Heredity
Takashi Okada, Xin Sun, Stephen McIlfatrick, Justin C. St John
Summary: This study investigated the influence of experimental and analysis conditions on the estimation of methylation levels in specific mtDNA sequences using BS-seq. The researchers found false positive non-CpG methylation in specific regions and identified the causes of these false methylation calls. They also confirmed the absence of CHH methylation in these regions.
NAR GENOMICS AND BIOINFORMATICS
(2022)