Article
Biochemistry & Molecular Biology
Haruna Tani, Kaori Ishikawa, Hiroaki Tamashiro, Emi Ogasawara, Takehiro Yasukawa, Shigeru Matsuda, Akinori Shimizu, Dongchon Kang, Jun-Ichi Hayashi, Fan-Yan Wei, Kazuto Nakada
Summary: This study established a mouse model carrying a pathogenic mutation in the mitochondrial tRNA gene, associated with metabolic syndrome-like symptoms. The mutation led to decreased protein levels and reduced Complex I activity in mitochondria, providing insights into the molecular basis of mutation-mediated mitochondrial disorders.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Majda Mehmedovic, Martial Martucci, Henrik Spahr, Layal Ishak, Anup Mishra, Maria Eugenia Sanchez-Sandoval, Carlos Pardo-Hernandez, Bradley Peter, Maria Sanchez-Sandoval, Siet M. van den Wildenberg, Maria Falkenberg, Geraldine Farge
Summary: This study provides a biochemical characterization of the pathogenic TFAM variant P178L and suggests that the mutation severely impairs mtDNA transcription initiation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Review
Obstetrics & Gynecology
Josef Finsterer
Summary: Polycystic ovary syndrome (PCOS) is a multi-causal condition. Variations in mitochondrial DNA (mtDNA) are increasingly recognized as one of the genetic causes of PCOS. PCOS is associated not only with known syndromic mitochondrial disorders but also with non-syndromic mitochondrial disorders, and even with mtDNA variants exclusively causing PCOS. Further studies are needed to establish the causal link between mtDNA variants and PCOS.
REPRODUCTIVE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniela Valenti, Fiorenza Stagni, Marco Emili, Sandra Guidi, Renata Bartesaghi, Rosa Anna Vacca
Summary: This study found that brain mitochondrial bioenergetic defects are present in Ts65Dn pups and early treatment with 7,8-DHF can positively impact mitochondrial function. These findings suggest the potential of 7,8-DHF as a translational treatment for neurodevelopmental alterations in Down syndrome.
Article
Cell Biology
Sanna Ryytty, Shalem R. Modi, Nikolay Naumenko, Anastasia Shakirzyanova, Muhammad Obaidur Rahman, Miia Vaara, Anu Suomalainen, Pasi Tavi, Riikka H. Hamalainen
Summary: The m.3243A>G mutation in mitochondrial tRNA-Leu(UUR) is a common pathogenic mutation in humans, but the causes for the clinical variability are unknown. In this study, iPSC-CMs derived from two different m.3243A>G patients were used to investigate the molecular effects of high mutation load on cardiomyocyte functionality. The results showed that high mutation load impaired mitochondrial respiration in both patients' cells, but the downstream consequences varied, suggesting the influence of other factors such as glucose metabolism, ATP levels, and intracellular calcium signaling.
Article
Cell Biology
Jae Min Cho, Seul-Ki Park, Rajeshwary Ghosh, Kellsey Ly, Caroline Ramous, Lauren Thompson, Michele Hansen, Maria Sara de Lima Coutinho Mattera, Karla Maria Pires, Maroua Ferhat, Sohom Mookherjee, Kevin J. Whitehead, Kandis Carter, Marcio Buffolo, Sihem Boudina, J. David Symons
Summary: Protein quality control mechanisms decline during cardiac aging, leading to accumulation of protein aggregates and organelle damage. However, late-in-life exercise training can improve autophagy, protein aggregate clearance, and overall heart function in old mice.
Article
Cell Biology
Xiaojia Huang, Xianming Zhang, Narsa Machireddy, Colin E. Evans, Shawn D. Trewartha, Guochang Hu, Yun Fang, Goekhan M. Mutlu, David Wu, You-Yang Zhao
Summary: Aging impairs endothelial regeneration and vascular repair, leading to increased mortality in acute respiratory distress syndrome (ARDS) after sepsis challenge. Reactivation of the FoxM1 gene or treatment with the DNA demethylating agent decitabine promotes endothelial regeneration, normalizes vascular repair and resolution of inflammation, and improves survival in aged mice. FOXM1 induction is impaired in elderly patients with ARDS, suggesting that targeting FoxM1-mediated endothelial regeneration may be a potential therapy for this population.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Inna Yu Vitkalova, Artem P. Gureev, Ekaterina A. Shaforostova, Olga N. Boyko, Abir U. Igamberdiev, Vasily N. Popov
Summary: Potatoes are a common crop worldwide but are highly susceptible to pests such as insects and fungi, with the use of pesticides affecting seed germination and plant growth. Research shows that some pesticides inhibit electron flow, while others uncouple the respiratory chain, leading to decreased membrane potential as the main negative effect of the studied pesticides.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Juliane Baumann, Laura Sachs, Otto Oliver, Ingmar Schoen, Peter Nestler, Carlo Zaninetti, Martin Kenny, Ruth Kranz, Hendrik von Eysmondt, Johanna Rodriguez, Tilman E. Schaeffer, Zoltan Nagy, Andreas Greinacher, Raghavendra Palankar, Markus Bender
Summary: Patients with MYH9-related disease have a tendency for increased bleeding due to reduced platelet forces caused by mutations. Activation of mutant platelets is comparable to controls, but phosphorylation of myosin light chain is reduced. Treatment with tranexamic acid can improve hemostatic function.
Article
Medicine, Research & Experimental
Paul Stamm, Ina Kirmes, Alexander Palmer, Michael Molitor, Miroslava Kvandova, Sanela Kalinovic, Dominika Mihalikova, George Reid, Philip Wenzel, Thomas Muenzel, Andreas Daiber, Thomas Jansen
Summary: This study found significant ROS production in the left heart of mice treated with DOX, but not in the right heart. Transcriptional changes differ between the left and right heart, correlating with myocardial dysfunction. The results emphasize the importance of evaluating parameters of left and right heart function during DOX therapy.
Article
Biochemistry & Molecular Biology
Liza Douiev, Chaya Miller, Guy Keller, Hadar Benyamini, Bassam Abu-Libdeh, Ann Saada
Summary: In this study, we demonstrated that COX4-1 deficiency leads to accumulative DNA damage and premature cellular senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Wei Wang, Ran Li, Wanying Miao, Cody Evans, Liping Lu, Jingjun Lyu, Xuan Li, David S. Warner, Xiaoping Zhong, Ulrike Hoffmann, Huaxin Sheng, Wei Yang
Summary: This study developed a validated mouse model of asphyxial CA and CPR. Using this model, it was demonstrated that asphyxial CA and CPR significantly impact both the nervous and immune systems, impairing lymphopoiesis of T and B cells.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Article
Pediatrics
Ana Lukic, Frederik Buchvald, Lone Agertoft, Sune Rubak, Marianne Skov, Michael Perch, Kim G. Nielsen
Summary: This study describes the national prevalence and characteristics of Danish children and adolescents with severely impaired lung function. The prevalence was found to be low, with cystic fibrosis being the most common diagnosis. Additionally, about 25% of the patients had elements of airway malformations or non-pulmonary conditions, which require clinical attention.
Article
Neurosciences
Kelly A. Rich, Megan G. Pino, Mehmet E. Yalvac, Ashley Fox, Hallie Harris, Maria H. H. Balch, W. David Arnold, Stephen J. Kolb
Summary: KIF5A is a motor protein responsible for axonal transport. Loss of function variants in the N-terminal domain are associated with hereditary spastic paraplegia and hereditary motor neuropathy, while gain of function splice-site variants in the C-terminal domain are associated with ALS.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Tom Kretzschmar, Mohamed M. Bekhite, Jasmine M. F. Wu, Daniela Haase, Martin Foerster, Tina Mueller, Sandor Nietzsche, Martin Westermann, Marcus Franz, Markus H. Graeler, P. Christian Schulze
Summary: The study reveals that Doxorubicin increases ceramide levels, leading to cell death and fibrosis, and that inhibiting ceramide synthesis can partially reverse the associated damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pediatrics
Karin Naess, Helene Bruhn, Henrik Stranneheim, Christoph Freyer, Rolf Wibom, Arnaud Mourier, Martin Engvall, Inger Nennesmo, Nicole Lesko, Anna Wredenberg, Anna Wedell, Ulrika von Dobeln
Summary: In this study, clinical and biochemical data from 55 pediatric patients with combined deficiencies of mitochondrial respiratory chain complexes were evaluated to establish genetic etiology. Disease onset was early in life, with common symptoms including muscle weakness, hypotonia, and developmental delay. Variants were found in 20 different nuclear genes and in mitochondrial DNA among the patients.
JOURNAL OF PEDIATRICS
(2021)
Article
Genetics & Heredity
Sandrina P. Correia, Marco F. Moedas, Karin Naess, Helene Bruhn, Camilla Maffezzini, Javier Calvo-Garrido, Nicole Lesko, Rolf Wibom, Florian A. Schober, Anders Jemt, Henrik Stranneheim, Christoph Freyer, Anna Wedell, Anna Wredenberg
Summary: In this case, a patient with a homozygous mutation in an intron region of the NDUFB7 gene had a primary complex I defect, presenting symptoms such as intrauterine growth restriction, hypertrophic cardiomyopathy, lactic acidosis, encephalopathy, and eventually leading to fatal outcome. The detected mutation resulted in reduced NDUFB7 protein levels and complex I activity, which were normalized through complementation studies with wild-type NDUFB7 expression in patient fibroblasts.
Article
Biochemical Research Methods
Florian A. Schober, Ilian Atanassov, David Moore, Javier Calvo-Garrido, Marco F. Moedas, Anna Wedell, Christoph Freyer, Anna Wredenberg
Summary: The SILAF method allows for efficient and in-depth proteomic analysis in Drosophila melanogaster, providing insights into metabolic regulation.
MOLECULAR & CELLULAR PROTEOMICS
(2021)
Article
Multidisciplinary Sciences
Florian A. Schober, David Moore, Ilian Atanassov, Marco F. Moedas, Paula Clemente, Akos Vegvari, Najla El Fissi, Roberta Filograna, Anna-Lena Bucher, Yvonne Hinze, Matthew The, Erik Hedman, Ekaterina Chernogubova, Arjana Begzati, Rolf Wibom, Mohit Jain, Roland Nilsson, Lukas Kall, Anna Wedell, Christoph Freyer, Anna Wredenberg
Summary: The gradual decline in mitochondrial SAM levels leads to defects in mitochondrial function, including loss of metabolites and impaired assembly of the oxidative phosphorylation system. These findings demonstrate the importance of cellular methylation potential for energy metabolism, with direct relevance for pathophysiology, aging, and cancer.
Article
Genetics & Heredity
Henrik Stranneheim, Kristina Lagerstedt-Robinson, Mans Magnusson, Malin Kvarnung, Daniel Nilsson, Nicole Lesko, Martin Engvall, Britt-Marie Anderlid, Henrik Arnell, Carolina Backman Johansson, Michela Barbaro, Erik Bjorck, Helene Bruhn, Jesper Eisfeldt, Christoph Freyer, Giedre Grigelioniene, Peter Gustavsson, Anna Hammarsjo, Maritta Hellstrom-Pigg, Erik Iwarsson, Anders Jemt, Mikael Laaksonen, Sara Lind Enoksson, Helena Malmgren, Karin Naess, Magnus Nordenskjold, Mikael Oscarson, Maria Pettersson, Chiara Rasi, Adam Rosenbaum, Ellika Sahlin, Eliane Sardh, Tommy Stodberg, Bianca Tesi, Emma Tham, Hakan Thonberg, Virpi Tohonen, Ulrika von Dobeln, Daphne Vassiliou, Sofie Vonlanthen, Ann-Charlotte Wikstrom, Josephine Wincent, Ola Winqvist, Anna Wredenberg, Sofia Ygberg, Rolf H. Zetterstrom, Per Marits, Maria Johansson Soller, Ann Nordgren, Valtteri Wirta, Anna Lindstrand, Anna Wedell
Summary: The study reports findings from whole genome sequencing of 4437 individuals at the Genomic Medicine Center Karolinska-Rare Diseases (GMCK-RD) since mid-2015, leading to molecular diagnoses for a portion of patients. Information sharing between teams was beneficial in clinical practice. Additionally, research resulted in the discovery of 17 new disease-causing genes.
Article
Biochemistry & Molecular Biology
Mara Mennuni, Roberta Filograna, Andrea Felser, Nina A. Bonekamp, Patrick Giavalisco, Oleksandr Lytovchenko, Nils-Goran Larsson
Summary: Resistance to mitochondrial transcription inhibitors (IMTs) is mainly achieved through compensatory increase in mitochondrial DNA expression and cellular metabolites. Loss of genes related to von Hippel-Lindau and mTORC1 pathways confers resistance to the inhibitors. Downregulation of mitochondrial transcription factor A and inhibition of mitochondrial translation also impairs survival of resistant cells.
Article
Biochemistry & Molecular Biology
Florian A. Schober, Jia Xin Tang, Kate Sergeant, Marco F. Moedas, Charlotte M. Zierz, David Moore, Conrad Smith, David Lewis, Nishan Guha, Sila Hopton, Gavin Falkous, Amanda Lam, Angela Pyle, Joanna Poulton, Grainne S. Gorman, Robert W. Taylor, Christoph Freyer, Anna Wredenberg
Summary: The SLC25A26 gene mutation can cause mitochondrial disease with varying symptoms at different ages. In this study, we reported two cases of adult patients and speculated, based on mouse and fruit fly models, that the impairment of SAH transport across the mitochondrial membrane may lead to milder, late-onset phenotypes.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Meenakshi Singh, Viktor Posse, Bradley Peter, Maria Falkenberg, Claes M. Gustafsson
Summary: This study demonstrates that misincorporated ribonucleotides (rNMPs) in human mitochondrial genome can affect mitochondrial transcription, especially when they are present in consecutive stretches. This finding suggests that impaired transcription may be associated with genetic disorders characterized by imbalanced nucleotide pools and higher levels of embedded rNMPs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Xuefeng Zhu, Xie Xie, Hrishikesh Das, Benedict G. Tan, Yonghong Shi, Ali Al-Behadili, Bradley Peter, Elisa Motori, Sebastian Valenzuela, Viktor Posse, Claes M. Gustafsson, B. Martin Haellberg, Maria Falkenberg
Summary: The non-coding RNA molecule 7S RNA regulates mitochondrial transcription in mammalian cells by inducing POLRMT dimerization, which prevents transcription initiation.
Article
Genetics & Heredity
Dusanka Milenkovic, Adrian Sanz-Moreno, Julia Calzada-Wack, Birgit Rathkolb, Oana Veronica Amarie, Raffaele Gerlini, Antonio Aguilar-Pimentel, Jelena Misic, Marie-Lune S. Simard, Eckhard T. Wolf, Helmut S. Fuchs, Valerie T. Gailus-Durner, Martin Hrabe S. de Angelis, Nils-Goeran T. Larsson
Summary: The authors addressed the controversy surrounding the role of the mitochondrial genome and MGME1 in mtDNA metabolism by studying knockout mice. They found that loss of MGME1 leads to the formation of linear deleted mtDNA fragments, contradicting previous reports. In addition, aged knockout mice developed various age-associated pathologies, including weight loss, cataract, retinopathy, kidney inflammation, glomerular changes, fibrosis, and nephrotic syndrome. These findings suggest that defective mtDNA replication can trigger an immune response and cause progressive pathology in aging kidneys.
Article
Biochemistry & Molecular Biology
Jelena Misic, Dusanka Milenkovic, Ali Al-Behadili, Xie Xie, Min Jiang, Shan Jiang, Roberta Filograna, Camilla Koolmeister, Stefan J. Siira, Louise Jenninger, Aleksandra Filipovska, Anders R. Clausen, Leonardo Caporali, Maria Lucia Valentino, Chiara La Morgia, Valerio Carelli, Thomas J. Nicholls, Anna Wredenberg, Maria Falkenberg, Nils-Goran Larsson
Summary: RNase H1 plays an essential role in mammalian mitochondria, particularly in the processing of RNA primers and regulation of mtDNA replication. Loss of RNase H1 leads to impaired mtDNA replication and depletion, as well as the formation of abnormal mtDNA molecules.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Paula Clemente, Javier Calvo-Garrido, Sarah F. Pearce, Florian A. Schober, Megumi Shigematsu, Stefan J. Siira, Isabelle Laine, Henrik Spahr, Christian Steinmetzger, Katja Petzold, Yohei Kirino, Rolf Wibom, Oliver Rackham, Aleksandra Filipovska, Joanna Rorbach, Christoph Freyer, Anna Wredenberg
Summary: Using Drosophila and mouse models, this study demonstrates that non-canonical RNA processing in mammalian mitochondria results in the formation of 3' phosphates, which are hydrolyzed by the phosphatase activity of the carbon catabolite repressor 4 domain-containing family member ANGEL2. The findings also suggest the involvement of the FAST kinase domain-containing protein family in the generation of these 3' phosphates.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Laura S. Kremer, Lyuba V. Bozhilova, Diana Rubalcava-Gracia, Roberta Filograna, Mamta Upadhyay, Camilla Koolmeister, Patrick F. Chinnery, Nils-Goran Larsson
Summary: In this study, the role of autophagy in germline purifying selection of mtDNA was investigated by mating different autophagy-deficient mouse models with mice carrying a pathogenic tRNA(Ala) gene mutation. The results showed that Bcl2l13 had a significant effect on the selection process, while Ulk1 and Ulk2 had weaker effects, and Parkin had no statistically significant impact. This study provides experimental evidence for the distinct roles of autophagy in germline purifying selection of mtDNA and establishes a framework for future studies on this process.
Article
Biology
Fynn M. Hansen, Laura S. Kremer, Ozge Karayel, Isabell Bludau, Nils-Goeran Larsson, Inge Kuehl, Matthias Mann
Summary: Mitochondria are essential organelles with tissue-specific functions, and phosphorylation plays an important role in regulating these functions. This study used mass spectrometry to quantitatively analyze the protein and phosphoprotein profiles of mitochondria from different tissues. The results provide a comprehensive map of mitochondrial proteins and phosphorylation events, and reveal tissue-specific regulation at the phosphoproteome level. The study reproduces known phosphorylation events and identifies new phosphorylation clusters associated with mitochondrial fusion.
LIFE SCIENCE ALLIANCE
(2023)
Article
Endocrinology & Metabolism
Michael P. Murphy, Hulya Bayir, Vsevolod Belousov, Christopher J. Chang, Kelvin J. A. Davies, Michael J. Davies, Tobias P. Dick, Toren Finkel, Henry J. Forman, Yvonne Janssen-Heininger, David Gems, Valerian E. Kagan, Balaraman Kalyanaraman, Nils-Goran Larsson, Ginger L. Milne, Thomas Nystrom, Henrik E. Poulsen, Rafael Radi, Holly Van Remmen, Paul T. Schumacker, Paul J. Thornalley, Shinya Toyokuni, Christine C. Winterbourn, Huiyong Yin, Barry Halliwell
Summary: This article discusses the important roles of reactive oxygen species (ROS) in health and disease, and proposes guidelines and best practices for the nomenclature and assessment of ROS, oxidative reactions, and oxidative damage in cells, tissues, and in vivo.