Article
Multidisciplinary Sciences
Nicole Kleiber, Nicolas Lemus-Diaz, Carina Stiller, Marleen Heinrichs, Mandy Mong-Quyen Mai, Philipp Hackert, Ricarda Richter-Dennerlein, Claudia Hoebartner, Katherine E. Bohnsack, Markus T. Bohnsack
Summary: RNA modifications, specifically the enzyme METTL8, play a crucial role in regulating RNA functions and have significant impacts on tRNA structure and mitochondrial translation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Irene Vercellino, Leonid A. Sazanov
Summary: The enzymes of the mitochondrial electron transport chain play a vital role in cell metabolism, forming supercomplexes in vivo. The assembly factor SCAF1 is crucial in mediating the assembly of CIII2CIV, but not involved in the assembly of the respirasome. Assembling into supercomplexes enhances the catalytic efficiency of CIII2 and CIV, potentially fine tuning the electron transfer efficiency in the electron transport chain.
Article
Reproductive Biology
Karine Dubuc, Mathilde Marchais, Isabelle Gilbert, Alexandre Bastien, Karen E. Nenonene, Edward W. Khandjian, Robert S. Viger, Geraldine Delbes, Claude Robert
Summary: The study found that m(6)A methylation in stored mRNA is higher in oocytes than in somatic cells, indicating its importance in early embryo development. Furthermore, the expression and localization patterns of epitranscriptome machinery in ovaries and oocytes differ among different mammalian species, suggesting a species-specific regulation of RNA during the oocyte transcriptional silencing period.
JOURNAL OF OVARIAN RESEARCH
(2023)
Review
Biochemical Research Methods
Sophia Hsin-Jung Li, Michel Nofal, Lance R. Parsons, Joshua D. Rabinowitz, Zemer Gitai
Summary: The study provides an optimized ribosome profiling protocol (MitoRiboSeq) for investigating mitochondrial translation in mammalian cells, highlighting the importance of studying translation within mitochondria.
Review
Biochemistry & Molecular Biology
Katja E. Menger, Alejandro Rodriguez-Luis, James Chapman, Thomas J. Nicholls
Summary: Mitochondrial genome (mtDNA) is a small DNA molecule present in human cells, playing a crucial role in mitochondrial gene expression and function. Topoisomerases are enzymes that modulate mtDNA topology, impacting mitochondrial function. Loss of topoisomerase activity can lead to defects in mitochondrial function.
Review
Genetics & Heredity
Oliver Rackham, Aleksandra Filipovska
Summary: The mitochondrial genome encodes core subunits essential for energy conversion. New technologies and disease models provide deeper insights into mitochondrial genome organization and expression, as well as diseases caused by impaired energy conversion.
NATURE REVIEWS GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Gustavo Carvalho, Bruno Marcal Repoles, Isabela Mendes, Paulina H. Wanrooij
Summary: Research has focused on maintenance and instability of mitochondrial DNA, exploring the role of DNA repair factors in mitochondria and the connection between mtDNA damage and immune response. Future studies should delve into mechanisms by which mitochondria maintain mtDNA, the balance between repair and degradation, as well as the release of mtDNA into the cytosol.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Biochemistry & Molecular Biology
Stephen P. Burr, Florian Klimm, Angelos Glynos, Malwina Prater, Pamella Sendon, Pavel Nash, Christopher A. Powell, Marie-Lune Simard, Nina A. Bonekamp, Julia Charl, Hector Diaz, Lyuba V. Bozhilova, Yu Nie, Haixin Zhang, Michele Frison, Maria Falkenberg, Nick Jones, Michal Minczuk, James B. Stewart, Patrick F. Chinnery
Summary: Mitochondrial activity varies between organs, and lineage-specific expression profiles of essential mitochondrial genes emerge early in mouse development. Disrupting intra-mitochondrial protein synthesis with mtDNA mutations induces cell lineage-specific compensatory responses, including novel molecular pathways not previously associated with organellar maintenance. These compensatory pathways, regulated by transcription factors promoting organelle resilience, contribute to tissue specificity in mitochondrial diseases and may be potential targets for organ-directed treatments.
Article
Multidisciplinary Sciences
Ying Wang, Frederick S. Yen, Xiphias Ge Zhu, Rebecca C. Timson, Ross Weber, Changrui Xing, Yuyang Liu, Benjamin Allwein, Hanzhi Luo, Hsi-Wen Yeh, Soren Heissel, Gokhan Unlu, Eric R. Gamazon, Michael G. Kharas, Richard Hite, Kivanc Birsoy
Summary: SLC25A39 is identified as a regulator of GSH transport into mitochondria, and its loss affects mitochondrial GSH import and abundance without impacting cellular GSH levels. Its absence also leads to defects in the activity and stability of proteins containing iron-sulfur clusters, and mitochondrial GSH import is found to be essential for cell proliferation and red blood cell development.
Review
Geriatrics & Gerontology
Xiaoxian Xie, Ruonan Shu, Chunan Yu, Zhengwei Fu, Zezhi Li
Summary: Mitochondrial dysfunction plays a crucial role in various diseases, and AKT, as a serine/threonine kinase, exerts important roles in cell metabolism and oxidative state regulation through modulating different mechanisms related to mitochondria.
Article
Multidisciplinary Sciences
Adrien Leger, Paulo P. Amaral, Luca Pandolfini, Charlotte Capitanchik, Federica Capraro, Valentina Miano, Valentina Migliori, Patrick Toolan-Kerr, Theodora Sideri, Anton J. Enright, Konstantinos Tzelepis, Folkert J. van Werven, Nicholas M. Luscombe, Isaia Barbieri, Jernej Ule, Tomas Fitzgerald, Ewan Birney, Tommaso Leonardi, Tony Kouzarides
Summary: Nanocompore is a new methodology for modification detection from Nanopore data, utilizing comparison between RNA samples of interest and non-modified control samples to identify modifications with positional accuracy in vitro and applicable to human and yeast RNA research.
NATURE COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Viktoriia A. Arzumanian, Georgii Dolgalev, Ilya Y. Kurbatov, Olga Kiseleva, Ekaterina Poverennaya
Summary: The building blocks for RNA molecules have a larger diversity than the standard four nucleotides due to post-transcriptional biochemical modifications. These modifications, both essential for RNA functions and functioning as dynamic markings, form the epitranscriptome. Over 300 distinct RNA modifications from all three life domains have been identified, but most reviews only cover a few well-established modifications. This study provides a comprehensive overview of the current research status on the epitranscriptome, analyzing the available information for all known RNA modifications and describing the current status of research on most RNA modifications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Dalen Zuidema, Alexis Jones, Won-Hee Song, Michal Zigo, Peter Sutovsky
Summary: The degradation of sperm-borne mitochondria after fertilization, known as post-fertilization sperm mitophagy, ensures exclusive maternal inheritance of mitochondrial DNA. This process involves the ubiquitin-proteasome system and other autophagic cofactors. The study used mass spectrometry and a porcine cell-free system to identify proteins involved in post-fertilization sperm mitophagy. The findings confirm the involvement of known determinants and provide a list of candidate cofactors for future studies.
Review
Engineering, Biomedical
Zhen Bouman Chen, Ming He, Julie Yi-Shuan Li, John Y. -J. Shyy, Shu Chien
Summary: The central dogma of gene expression involves DNA transcription to RNA and RNA translation into protein. RNA undergoes various forms of modifications termed epitranscriptional regulations, leading to functional changes. Recent studies have shown important roles of RNA modifications in gene translation, DNA damage response, and cell fate regulation. Elucidation of epitranscriptional modifications in the cardiovascular system is crucial for understanding cardiovascular physiology and pathophysiology, and this review provides an overview of the epitranscriptome landscape, key concepts, recent findings, and analysis tools in this field, with potential applications in biomedical engineering research.
ANNUAL REVIEW OF BIOMEDICAL ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Jinke Gu, Tianya Liu, Runyu Guo, Laixing Zhang, Maojun Yang
Summary: Cryo-EM structures of the porcine respiratory complex I reveal the binding and reduction mechanism of Q10 in the Q chamber. The study proposes a 'two-Q' model for the coupling mechanism of complex I. The findings overturn the widely accepted previous proposal and provide new insights into the structure and function of complex I.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Petra Palenikova, Michael E. Harbour, Shujing Ding, Ian M. Fearnley, Lindsey Van Haute, Joanna Rorbach, Rick Scavetta, Michal Minczuk, Pedro Rebelo-Guiomar
Summary: The method described utilizes density separation and mass spectrometric quantitation for quantitative analysis of native protein or ribonucleoprotein complexes, with the ComPrAn software package providing tools for data organization, analysis, and visualization. This technology can be applied to study the assembly and dynamic properties of macromolecular complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Review
Genetics & Heredity
Pedro Silva-Pinheiro, Michal Minczuk
Summary: Mitochondria are controlled by both nuclear DNA and their own genome, mtDNA, with mutations in mtDNA potentially leading to devastating hereditary diseases. Recent advancements in genetic modification of mammalian mtDNA show promise in using genome editing technologies for treating mitochondrial diseases.
NATURE REVIEWS GENETICS
(2022)
Article
Multidisciplinary Sciences
Pedro Rebelo-Guiomar, Simone Pellegrino, Kyle C. Dent, Aldema Sas-Chen, Leonor Miller-Fleming, Caterina Garone, Lindsey Van Haute, Jack F. Rogan, Adam Dinan, Andrew E. Firth, Byron Andrews, Alexander J. Whitworth, Schraga Schwartz, Alan J. Warren, Michal Minczuk
Summary: A study on the human mitochondrial transcriptome reveals that 2'-O-methylation is limited to specific residues of the mitoribosomal large subunit, and the modifications are dependent on different proteins. MRM2 plays a role in regulating mitochondrial respiration through mitoribosome biogenesis, but its methyltransferase activity is not essential for this process.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pedro Silva-Pinheiro, Pavel A. Nash, Lindsey Van Haute, Christian D. Mutti, Keira Turner, Michal Minczuk
Summary: Mutations in mitochondrial DNA can lead to clinically heterogeneous diseases. Here the authors demonstrate in vivo base editing of mouse mitochondrial DNA in a post-mitotic tissue by AAV delivery of DddA-derived cytosine base editor (DdCBE).
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Benedict G. Tan, Christian D. Mutti, Yonghong Shi, Xie Xie, Xuefeng Zhu, Pedro Silva-Pinheiro, Katja E. Menger, Hector Diaz-Maldonado, Wei Wei, Thomas J. Nicholls, Patrick F. Chinnery, Michal Minczuk, Maria Falkenberg, Claes M. Gustafsson
Summary: The discovery of a second light strand promoter (LSP2) in the human mitochondrial genome expands our understanding of mitochondrial gene expression by allowing replication and gene expression to be orchestrated from two distinct sites.
Article
Clinical Neurology
Micol Falabella, Michal Minczuk, Michael G. Hanna, Carlo Viscomi, Robert D. S. Pitceathly
Summary: Successful clinical trials of gene therapy for Leber hereditary optic neuropathy have raised hopes for genetic therapies for other primary mitochondrial diseases (PMDs). However, obstacles remain for the clinical application of genetic therapies in PMDs, with crucial need for innovative, safe and effective genome editing technologies and vectors.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Julian C. W. Willis, Pedro Silva-Pinheiro, Lily Widdup, Michal Minczuk, David R. Liu
Summary: DddA-derived cytosine base editors, specifically zinc finger DdCBEs, have been developed and optimized to improve their editing performance in organelle and nuclear DNA. These findings demonstrate a compact, all-protein base editing research tool for precise editing without double-strand breaks.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Pedro Silva-Pinheiro, Christian D. Mutti, Lindsey Van Haute, Christopher A. Powell, Pavel A. Nash, Keira Turner, Michal Minczuk
Summary: The study developed a DNA editor called MitoKO, which can precisely eliminate each protein-coding gene in the mouse mitochondrial genome. MitoKO was used to generate knockout cells with high homoplasmy levels in vitro and a mouse model with high heteroplasmy levels and no off-target edits. This tool will aid in the comprehensive investigation of mtDNA-related pathways and the creation of clinically relevant in vivo models of mtDNA dysfunction.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Maria Lambros, Jonathan Moreno, Qinqin Fei, Cyrus Parsa, Robert Orlando, Lindsey Van Haute
Summary: Oral mucositis is a common side effect of cancer treatment, especially with the mTORC1 inhibitor everolimus. Current treatment methods are not effective enough, so a better understanding of the causes and mechanisms behind oral mucositis is needed to find potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Lindsey Van Haute, Emily O'Connor, Hector Diaz-Maldonado, Benjamin Munro, Kiran Polavarapu, Daniella H. Hock, Gautham Arunachal, Alkyoni Athanasiou-Fragkouli, Mainak Bardhan, Magalie Barth, Dominique Bonneau, Nicola Brunetti-Pierri, Gerarda Cappuccio, Nikeisha J. Caruana, Natalia Dominik, Himanshu Goel, Guy Helman, Henry Houlden, Guy Lenaers, Karine Mention, David Murphy, Bevinahalli Nandeesh, Catarina Olimpio, Christopher A. Powell, Veeramani Preethish-Kumar, Vincent Procaccio, Rocio Rius, Pedro Rebelo-Guiomar, Cas Simons, Seena Vengalil, Maha S. Zaki, Alban Ziegler, David R. Thorburn, David A. Stroud, Reza Maroofian, John Christodoulou, Claes Gustafsson, Atchayaram Nalini, Hanns Lochmueller, Michal Minczuk, Rita Horvath
Summary: TEFM gene mutations are associated with mitochondrial respiratory chain deficiency and a wide range of clinical presentations, including a treatable neuromuscular transmission defect. The affected individuals show reduced levels of mitochondrial RNA transcripts in muscle and primary fibroblasts. Knockdown of tefm gene in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function, further supporting the genotype-phenotype correlation.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Petra Palenikova, Michal Minczuk, Pedro Rebelo-Guiomar
Summary: This study presents a flexible setup for the analysis of dynamic macromolecular complexes in near-native conditions. The human mitochondrial ribosome was analyzed using density gradient ultracentrifugation coupled to quantitative mass spectrometry, providing standardized analysis of the complex.
Article
Biochemistry & Molecular Biology
Damien Marchese, Florent Guislain, Tamara Pringels, Laure Bridoux
Summary: Homopolymeric amino acid repeats are common in human proteins, particularly in transcription factors and kinases. This study focuses on homopolymeric histidine repeats (polyH) and their role in regulating embryonic development. Through bioinformatic analysis, the study identifies that polyH-containing proteins interact with cysteine-rich proteins and proteins containing cysteine repeats. The study further investigates the HOXA1 protein, a transcription factor with a long polyH motif, and finds that the polyH motif is necessary for its interaction with cysteine-rich proteins. Additionally, the study discovers that metal ions are required for the HOXA1-MDFI interaction and identifies three polyH interactors that down-regulate the transcriptional activity of HOXA1.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2024)
