Article
Multidisciplinary Sciences
Salome Aeschlimann, Ana Kalichava, Bernd Schimanski, Bianca Manuela Berger, Clirim Jetishi, Philip Stettler, Torsten Ochsenreiter, Andre Schneider
Summary: This study revealed the structure and function of the exclusion zone filament (EZF) of the tripartite attachment complex (TAC). The p197 protein, the only known component of the EZF, was found to connect the mitochondrial outer membrane and the flagellum basal body. The N and C termini of p197 interacted with the peripheral OM protein TAC65 and the mature and probasal body, respectively, while the central region likely acted as a flexible spacer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Migla Miskinyte, John C. Dawson, Ashraff Makda, Dahlia Doughty-Shenton, Neil O. Carragher, Achim Schnaufer
Summary: In this study, we developed a high-content screen for pharmacologically induced kDNA loss in kinetoplastid parasites and identified a novel kDNA-targeting compound as a validated hit.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Simona Amodeo, Irina Bregy, Anneliese Hoffmann, Albert Fradera-Sola, Mara Kern, Helene Baudouin, Benoit Zuber, Falk Butter, Torsten Ochsenreiter
Summary: Trypanosoma brucei is a single-celled eukaryotic parasite with a unique mitochondrial genome called kinetoplast DNA (kDNA). The kDNA is physically linked to the basal body via the Tripartite Attachment Complex (TAC) to ensure its proper inheritance. In this study, we identified TbmtHMG44 and TbKAP68 as novel candidates that connect the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 leads to kDNA loss without missegregation, indicating their importance in maintaining the stability of the kDNA-TAC interface. These findings suggest that TbmtHMG44 and TbKAP68 form a distinct complex between the kDNA and TAC.
Article
Cell Biology
Simona Amodeo, Ana Kalichava, Albert Fradera-Sola, Eloise Bertiaux-Lequoy, Paul Guichard, Falk Butter, Torsten Ochsenreiter
Summary: Proper inheritance of the mitochondrial genome is crucial for eukaryotic cell survival. Trypanosoma brucei, a protozoan parasite, has a unique mitochondrial genome known as kinetoplast (k)DNA, which is anchored to the basal body by the tripartite attachment complex (TAC) to ensure proper segregation. The TAC-associated protein TAP110 plays a role in the separation of replicated kDNA networks and interacts with kDNA after assembly into the TAC region, shedding light on the connection between replication and segregation in different cellular compartments.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Yi-Tian Fu, Suleman, Chaoqun Yao, Hui-Mei Wang, Wei Wang, Guo-Hua Liu
Summary: This study sequenced the mitochondrial genome of the buffalo louse Haematopinus tuberculatus using next-generation sequencing. The results showed that the mt genome of H. tuberculatus consists of ten circular minichromosomes with varying gene numbers, which is different from other sucking lice species. The study also observed gene translocation and merger of mt minichromosomes in Haematopinus. The phylogeny generated from mt genome datasets showed a different topology compared to previous studies, indicating the need for additional data to resolve the phylogeny of sucking lice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Anu Hangas, Nina J. Kekalainen, Alisa Potter, Craig Michell, Kauko J. Aho, Chiara Rutanen, Johannes N. Spelbrink, Jaakko L. Pohjoismaki, Steffi Goffart
Summary: This study investigates the role of Topoisomerase 3 alpha (Top3 alpha) in mitochondrial DNA (mtDNA) replication and transcription. The findings suggest that Top3 alpha not only participates in mtDNA segregation but also supports the progression of the replication fork. Knockdown of Top3 alpha leads to replication fork stalling, increased mtDNA catenation, and decreased mtDNA levels. Overexpression, on the other hand, induces double-strand breaks and early replication termination while improving the resolution of mtDNA replication termination intermediates. Both knockdown and overexpression of Top3 alpha affect mitochondrial RNA transcription, resulting in a decrease in steady-state levels of mitochondrial transcripts.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biology
Domenico Giosa, Daniele Lombardo, Cristina Musolino, Valeria Chines, Giuseppina Raffa, Francesca Casuscelli di Tocco, Deborah D'Aliberti, Giuseppe Caminiti, Carlo Saitta, Angela Alibrandi, Riccardo Aiese Cigliano, Orazio Romeo, Giuseppe Navarra, Giovanni Raimondo, Teresa Pollicino
Summary: Using a high-throughput HBV integration sequencing method and bioinformatics, the researchers profiled HBV integration events in liver tissues from hepatocellular carcinoma patients. They found that HBV often integrates into mitochondrial DNA. The study revealed 3339 HBV integration sites, with a significant enrichment of clonal HBV integrations in the mitochondrial DNA, especially in the oxidative phosphorylation genes and D-loop region. The researchers also discovered that HBV RNA sequences can be imported into the mitochondria of hepatoma cells and may play a role in the process of HBV integration into mtDNA. These findings provide insights into the potential mechanism by which HBV integration contributes to HCC development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Heidi Foo, Anbupalam Thalamuthu, Jiyang Jiang, Forrest C. Koch, Karen A. Mather, Wei Wen, Perminder S. Sachdev
Summary: In this study, genetics of weighted functional brain network graph theory measures from 18,445 UK Biobank participants were investigated, revealing low heritability and high genetic correlations among the eighteen measures. A genome-wide significant locus was associated with the strength of specific networks. Further analysis showed phenotypic associations with sleep duration and insomnia in relation to somatomotor network strength.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Haixin Zhang, Marco Esposito, Mikael G. Pezet, Juvid Aryaman, Wei Wei, Florian Klimm, Claudia Calabrese, Stephen P. Burr, Carolina H. Macabelli, Carlo Viscomi, Mitinori Saitou, Marcos R. Chiaratti, James B. Stewart, Nick Jones, Patrick F. Chinnery
Summary: Heteroplasmic mitochondrial DNA mutations play a significant role in inherited diseases, with a few recurrent mutations accounting for the majority of cases. The preferential transmission of these mutations and their maintenance at various levels may be key factors contributing to disease development.
Article
Biology
Andrea Volante, Juan Carlos Alonso, Kiyoshi Mizuuchi
Summary: This study focuses on the unique architecture of the pSM19035 partition complex and its interaction with nucleoid-bound ParA(pSM)-ATP. It reveals that the presence of four or more contiguous ParB(pSM)-binding sequence repeats in the parS(pSM) is required for the assembly of a stable ParA(pSM)-ParB(pSM) complex and efficient activation of ParA(pSM)-ATPase.
Article
Multidisciplinary Sciences
Amina Batool, Yaping Dai, Hongbin Ma, Sijie Yin
Summary: Industries are increasingly adopting unmanned and intelligent systems for efficient processing and monitoring of structures in various applications. However, accurately classifying electro-mechanical machinery components poses challenges due to their high intra- and inter-class similarity. This article introduces a new pooling method and classification model that outperforms existing models with a high accuracy rate of 98.15%. It has significant potential for industrial implementation.
Article
Endocrinology & Metabolism
Li Li, Devon M. Conradson, Vinita Bharat, Min Joo Kim, Chung-Han Hsieh, Paras S. Minhas, Amanda M. Papakyrikos, Aarooran Sivakumaran Durairaj, Anthony Ludlam, Katrin Andreasson, Linda Partridge, Michael A. Cianfrocco, Xinnan Wang
Summary: Redox signal transduction from the mitochondrial matrix to the cytosol is mediated through interaction between MIC60 and Miro, disrupting which can ameliorate oxidative stress in Drosophila. This signaling pathway regulates cellular responses, impacting mitochondrial function and extending lifespan in fruit flies, as well as providing benefits in multiple disease models.
Article
Engineering, Mechanical
Yongxing Song, Jingting Liu, Dazhuan Wu, Linhua Zhang
Summary: A novel weak feature extraction method based on multiple frequency bands demodulation was proposed for fault diagnosis of rotating machinery, showing superior performance compared to existing methods in both simulation analysis and applications. This method provides a reliable basis for weak fault signal extraction and has great engineering significance.
JOURNAL OF THE BRAZILIAN SOCIETY OF MECHANICAL SCIENCES AND ENGINEERING
(2021)
Article
Multidisciplinary Sciences
Nahuel Zamponi, Emiliano Zamponi, Sergio A. Cannas, Dante R. Chialvo
Summary: Evidence from models and experiments suggests that the networked structure observed in mitochondria emerges at the critical point of a phase transition controlled by fission and fusion rates. In this study, we provide a theoretical framework to interpret the scaling behavior of mitochondrial network quantities and validate it through experiments. The obtained scaling exponents are comparable with critical exponents from models and theory. Overall, we offer a universal description of the structural phase transition in mammalian mitochondria.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Sivaranjani Namasivayam, Rodrigo P. Baptista, Wenyuan Xiao, Erica M. Hall, Joseph S. Doggett, Karin Troell, Jessica C. Kissinger
Summary: The content and structure of mitochondrial genomes vary widely across the eukaryotic tree of life, with protists showing extreme examples. Here, the independent evolution of fragmented cytochrome genes in Toxoplasma and related tissue coccidia, as well as the evolution of a novel genome architecture consisting minimally of 21 sequence blocks totaling 5.9 kb, have been reported. Single-molecule Nanopore reads reveal both whole and fragmented cytochrome genes, while a definitive genome architecture of the mtDNA sequence remains elusive.
Article
Microbiology
Caroline E. Dewar, Aitor Casas-Sanchez, Constentin Dieme, Aline Crouzols, Lee R. Haines, Alvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer
Summary: This study demonstrates that efficient energy production through mitochondria is critical for the trypanosome's swimming ability and migration within the tsetse fly. Surprisingly, trypanosomes with impaired mitochondrial energy production are only mildly compromised in their ability to colonize the tsetse fly midgut. This study provides new insights into the complex mechanisms of trypanosome infection in tsetse flies.
Article
Biochemistry & Molecular Biology
Sinclair Cooper, Elizabeth S. Wadsworth, Achim Schnaufer, Nicholas J. Savill
Summary: The mitochondrial DNA of protists of order Kinetoplastida consists of thousands of interlinked circular molecules. It includes two types of molecules, minicircles and maxicircles. Minicircles encode guide RNA (gRNA) genes that mediate post-transcriptional editing of maxicircle encoded genes. The human sleeping sickness parasite Trypanosoma brucei has a diverse set of minicircle classes, some of which contain decaying remnants of once functional gRNA genes. The sequencing and annotation of minicircle classes in T. brucei subspecies and isolates have provided valuable data for understanding their structure and transcription.
Article
Parasitology
Djamila Boushaki, Julie Wallis, Frederik Van den Broeck, Achim Schnaufer
Summary: The study confirmed recent Trypanosoma infections in camels in Southern Algeria were caused by T. b. evansi type A, and introduced a newly designed PCR assay specific for this type, which is expected to be useful for diagnostic purposes in the community.
ACTA PARASITOLOGICA
(2022)
Article
Microbiology
Bernd Schimanski, Salome Aeschlimann, Philip Stettler, Sandro Kaeser, Maria Gomez-Fabra Gala, Julian Bender, Bettina Warscheid, F. -Nora Voegtle, Andre Schneider
Summary: The protist parasite Trypanosoma brucei has a complicated structure called tripartite attachment complex (TAC) that ensures the faithful segregation of the single unit genome, kinetoplast DNA (kDNA), in its single mitochondrion. The TAC consists of several subunits, including p166, which is anchored in the inner membrane. While p166 interacts with other TAC subunits and theoretically bridges the distance between the outer membrane and the kDNA, it is believed that there are additional TAC-associated proteins that loosely bind to non-functional p166 lacking the C-terminal 34 aa and keep it at the TAC. However, the binding of full length p166 alone is not sufficient to withstand the mechanical load imposed by the segregating basal bodies.
Article
Multidisciplinary Sciences
Kai Pascal Alexander Haenggeli, Andrew Hemphill, Norbert Mueller, Bernd Schimanski, Philipp Olias, Joachim Mueller, Ghalia Boubaker
Summary: In this study, single and duplex TaqMan qPCR methods were developed for the absolute quantification of integrated drug selectable marker mdhfr-ts in Toxoplasma gondii. The single TaqMan qPCR method should have twice the copy number of dhfr-ts as compared to WT parasites in KO parasites. The duplex TaqMan qPCR method can simultaneously amplify the dhfr-ts fragment and the 529-bp repeat element in T. gondii for accurate detection of KOs.
Article
Multidisciplinary Sciences
Salome Aeschlimann, Ana Kalichava, Bernd Schimanski, Bianca Manuela Berger, Clirim Jetishi, Philip Stettler, Torsten Ochsenreiter, Andre Schneider
Summary: This study revealed the structure and function of the exclusion zone filament (EZF) of the tripartite attachment complex (TAC). The p197 protein, the only known component of the EZF, was found to connect the mitochondrial outer membrane and the flagellum basal body. The N and C termini of p197 interacted with the peripheral OM protein TAC65 and the mature and probasal body, respectively, while the central region likely acted as a flexible spacer.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Julika Radecke, Raphaela Seeger, Anna Kadkova, Ulrike Laugks, Amin Khosrozadeh, Kenneth N. Goldie, Vladan Lucic, Jakob B. Sorensen, Benoit Zuber
Summary: This study used cryo-electron tomography to observe the intermediate steps following synaptic stimulation, and found that during the early fusion stage after stimulation, synaptic vesicles undergo morphological changes to establish contact with the plasma membrane. The subsequent late fusion stage results in fusion pore opening and collapse of the synaptic vesicles. These morphological observations likely correspond to the transition of synaptic vesicles from one functional pool to another.
Article
Microbiology
Andrea Corona Ramirez, Kang Soo Lee, Adolfo Odriozola, Marek Kaminek, Roman Stocker, Benoit Zuber, Pilar Junier
Summary: The production of specialized resting cells is a survival strategy developed by organisms to withstand unfavorable environmental factors. Five bacterial taxa are recognized to form specialized resting cells, and they are characterized by low metabolic activity and higher resistance to environmental stress. A cross-species comparison of bacterial sporulation reveals a lack of common chemical signature among the specialized resting cells, with each group having a unique signature. The use of Raman spectroscopy enables the isolation of endospores based on their specific chemical signatures.
Article
Neurosciences
Federica Pilotto, Christopher Douthwaite, Rim Diab, Xiaoqian Ye, Zahraa Al Qassab, Christoph Tietje, Meriem Mounassir, Adolfo Odriozola, Aishwarya Thapa, Ronald A. M. Buijsen, Sophie Lagache, Anne -Christine Uldry, Manfred Heller, Stefan Muller, Willeke M. C. van Roon-Mom, Benoit Zuber, Sabine Liebscher, Smita Saxena
Summary: Vulnerable neuronal populations in neurodegenerative diseases are characterized by toxic protein deposits and alterations in excitability and activity levels. Using in vivo two-photon imaging in Sca1 mice, it was found that an inhibitory circuit element (molecular layer interneurons) becomes prematurely hyperexcitable, compromising sensorimotor signals in the cerebellum. Chronic inhibition of these hyperexcitable interneurons delayed neuronal degeneration, reduced pathology, and improved motor deficits in Sca1 mice.
Article
Microbiology
Simona Amodeo, Irina Bregy, Anneliese Hoffmann, Albert Fradera-Sola, Mara Kern, Helene Baudouin, Benoit Zuber, Falk Butter, Torsten Ochsenreiter
Summary: Trypanosoma brucei is a single-celled eukaryotic parasite with a unique mitochondrial genome called kinetoplast DNA (kDNA). The kDNA is physically linked to the basal body via the Tripartite Attachment Complex (TAC) to ensure its proper inheritance. In this study, we identified TbmtHMG44 and TbKAP68 as novel candidates that connect the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 leads to kDNA loss without missegregation, indicating their importance in maintaining the stability of the kDNA-TAC interface. These findings suggest that TbmtHMG44 and TbKAP68 form a distinct complex between the kDNA and TAC.
Article
Chemistry, Organic
Jan Thiede, Simon Rothenbuhler, Ioan Iacovache, Simon M. Langenegger, Benoit Zuber, Robert Haner
Summary: This article presents the supramolecular self-assembly of pyrene-DNA conjugates into nanostructures. DNA functionalized with different types of pyrene isomers can self-assemble into nano-objects with various shapes. The research also constructs an artificial light-harvesting complex, which has implications for the design of photosynthetic devices.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Microbiology
Simona Amodeo, Irina Bregy, Torsten Ochsenreiter
Summary: This article summarizes the diversity of mitochondrial DNA replication and proposes a new replication model using Trypanosoma brucei as an example, providing a mechanism for the maintenance of mitochondrial genetic diversity.
FEMS MICROBIOLOGY REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Benoit Zuber, Vladan Lucic
Summary: Cryo-electron tomography is a powerful tool for high-resolution imaging of cellular components in their native state, with neurons proving to be a versatile system for studying both general cellular components and neuron-specific processes.
JOURNAL OF STRUCTURAL BIOLOGY-X
(2022)
Article
Chemistry, Organic
Simon Rothenbuehler, Adrian Gonzalez, Ioan Iacovache, Simon M. Langenegger, Benoit Zuber, Robert Haener
Summary: The supramolecular assembly of DNA conjugates with tetraphenylethylene (TPE) sticky ends into vesicular structures is studied in this research. The aggregation-induced emission (AIE) active TPE units are used to monitor the assembly process using fluorescence spectroscopy. The number of TPE modifications on the conjugates' overhangs influences the supramolecular assembly behavior, with a minimum of two TPE residues required for a well-defined assembly process. The designed DNA-based nanostructures offer customized functionalization for applications in DNA nanotechnology.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Microbiology
Caroline E. Dewar, Aitor Casas-Sanchez, Constentin Dieme, Aline Crouzols, Lee R. Haines, Alvaro Acosta-Serrano, Brice Rotureau, Achim Schnaufer
Summary: The single-celled parasite Trypanosoma brucei is transmitted by tsetse flies and its development in the fly's gut depends on efficient energy production by mitochondria.