Article
Multidisciplinary Sciences
Thomas D. Jackson, Jordan J. Crameri, Linden Muellner-Wong, Ann E. Frazier, Catherine S. Palmer, Luke E. Formosa, Daniella H. Hock, Kenji M. Fujihara, Tegan Stait, Alice J. Sharpe, David R. Thorburn, Michael T. Ryan, David A. Stroud, Diana Stojanovski
Summary: Sideroflexins (SFXNs) are a family of proteins that have different functions in mitochondrial biology. Loss of SFXN4 leads to complex I assembly defect and it interacts with the core components of the mitochondrial complex I intermediate assembly complex.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Michele Brischigliaro, Elena Frigo, Samantha Corra, Cristiano De Pitta, Ildiko Szabo, Massimo Zeviani, Rodolfo Costa
Summary: Mutations in BCS1L are a common cause of human mitochondrial disease related to complex III deficiency, with diverse clinical symptoms and multisystem involvement. Studying genetic manipulation of Bcs1 in fruit flies reveals its fundamental role in complex III biogenesis and offers novel models for BCS1L-related human mitochondrial diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Review
Biochemistry & Molecular Biology
Vincenzo Zara, Gabriella De Blasi, Alessandra Ferramosca
Summary: This study critically analyzes the assembly process of the cytochrome bc(1) complex in the mitochondrial respiratory chain of yeast. It highlights the complexity of this process, which involves multiple protein subunits and the formation of distinct sub-complexes. The results of this study provide important insights into the mechanism and function of the mitochondrial respiratory chain, and suggest new areas of investigation for future research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jonathan Schiller, Eike Laube, Ilka Wittig, Werner Kuehlbrandt, Janet Vonck, Volker Zickermann
Summary: Cryo-electron microscopy was used to determine the structure of assembly intermediates associated with NDUFAF1. It was found that NDUFAF1, together with ND2, NDUFC2, and CIA84, forms the nucleation point of the assembly pathway. The central subunit ND3 is locked in an assembly-competent conformation by NDUFAF1, and major rearrangements of central subunits are required for complex I maturation.
Article
Biochemistry & Molecular Biology
Tasnim Arroum, Marie-Theres Borowski, Nico Marx, Frank Schmelter, Martin Scholz, Olympia Ekaterini Psathaki, Michael Hippler, Jose Antonio Enriquez, Karin B. Busch
Summary: The mitochondrial respiratory or electron transport chain (ETC) and ATP synthase collaborate in the process of oxidative phosphorylation (OXPHOS) to convert reduction power into ATP. Supramolecular assemblies known as respiratory supercomplexes (SC) are formed by three out of the four ETC complexes to adapt to changing conditions. NDUFB10, a subunit of complex I, plays a role in complex I and supercomplex assembly as well as bioenergetics function. NDUFB10 knockout results in decreased SCAF1, reduced respiration, and mitochondrial membrane potential, potentially due to loss of proton pumping.
BIOLOGICAL CHEMISTRY
(2023)
Article
Food Science & Technology
Jun Wang, Xue Tang, Yipin Lu, Yingying Zheng, Fanhang Zeng, Wentao Shi, Peng Zhou
Summary: The study demonstrates that lycopene can alleviate myocardial dysfunction and energy metabolism issues induced by Dityrosine, by improving mitochondrial performance and reducing oxidative stress to enhance heart health.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Clinical Neurology
Omar Hikmat, Pirjo Isohanni, Nandaki Keshavan, Matteo P. Ferla, Elisa Fassone, Mary-Alice Abbott, Marcello Bellusci, Niklas Darin, David Dimmock, Daniele Ghezzi, Henry Houlden, Federica Invernizzi, Nazreen B. Kamarus Jaman, Manju A. Kurian, Eva Morava, Karin Naess, Juan Dario Ortigoza-Escobar, Sumit Parikh, Alessandra Pennisi, Giulia Barcia, Karin B. Tylleskar, Damien Brackman, Saskia B. Wortmann, Jenny C. Taylor, Laurence A. Bindoff, Vineta Fellman, Shamima Rahman
Summary: This study delineates the full phenotypic spectrum of BCS1L-related disease, identifies the correlations between age of onset, specific variants, and clinical manifestations, and associates early presentation with poor prognosis. The presence of the c.232A>G (p.Ser78Gly) variant is significantly linked to worse survival outcomes, while other pathogenic BCS1L variants are more common in patients with later symptom onset.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Oncology
Danilo Swann Matassa, Daniela Criscuolo, Rosario Avolio, Ilenia Agliarulo, Daniela Sarnataro, Consiglia Pacelli, Rosella Scrima, Alessandra Colamatteo, Giuseppe Matarese, Nazzareno Capitanio, Matteo Landriscina, Franca Esposito
Summary: This study investigates the role of TRAP1 in cancer cell metabolism and reveals that TRAP1 regulates the activity of complex III, thereby affecting oxidative phosphorylation in cancer cells. Additionally, the components of complex III are found to be correlated with the response to cancer therapy and survival rates, implying the potential of complex III as a therapeutic target.
CANCER CELL INTERNATIONAL
(2022)
Article
Cell Biology
Katarzyna Justyna Chojnacka, Praveenraj Elancheliyan, Ben Hur Marins Mussulini, Karthik Mohanraj, Sylvie Callegari, Aleksandra Gosk, Tomasz Banach, Tomasz Goral, Karolina Szczepanowska, Peter Rehling, Remigiusz Adam Serwa, Agnieszka Chacinska
Summary: OCIAD2 is identified as an assembly factor for CIII2, playing an important role in the mitochondrial inner membrane. It interacts with ETC proteins and its loss leads to abnormal mitochondrial morphology, decreased CIII2 and supercomplex III2+IV, and reduced CIII enzymatic activity. This finding provides new insights into the biogenesis and architecture of the ETC.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Review
Cell Biology
Stefan Geldon, Erika Fernandez-Vizarra, Kostas Tokatlidis
Summary: Mitochondria are double-membrane organelles that participate in cellular respiration through the oxidative phosphorylation system, with most proteins encoded in the nucleus and imported to different compartments. The intermembrane space of mitochondria contains diverse proteins crucial for the maturation and function of electron transport chain complexes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Irene Hana Flones, Harald Nyland, Dagny-Ann Sandnes, Guido Werner Alves, Ole-Bjorn Tysnes, Charalampos Tzoulis
Summary: Early alpha-synuclein aggregation is associated with mitochondrial respiratory complex I (CI) deficiency in neurons of idiopathic Parkinson's disease (iPD), and there is selective loss of neurons affected by both pathologies.
Article
Chemistry, Medicinal
Keisuke Komatsuya, Takaya Sakura, Kazuro Shiomi, Satoshi Omura, Kenji Hikosaka, Tomoyoshi Nozaki, Kiyoshi Kita, Daniel Ken Inaoka
Summary: The mitochondrial electron transport chain of Plasmodium falciparum has been identified as a promising target for chemotherapy, with two enzymes and complex II considered as candidate drug targets. Siccanin has been discovered as a potent inhibitor of complex II and III in P. falciparum, showing no inhibition of corresponding complexes in mammalian mitochondria. This compound has a dual mechanism of action and is a potential candidate for the development of new antimalarial drugs.
Review
Chemistry, Medicinal
Jonathan Schiller, Volker Zickermann
Summary: This article summarizes the structure and redox mechanism of respiratory complex I, as well as the binding modes and inhibitory mechanisms of inhibitors in the Q reduction site and Q access pathway. It provides important insights into the crucial protein complex involved in mitochondrial oxidative phosphorylation.
Article
Biochemistry & Molecular Biology
Shafqat Rasool, Simon Veyron, Naoto Soya, Mohamed A. Eldeeb, Gergely L. Lukacs, Edward A. Fon, Jean-Francois Trempe
Summary: Mutations in PINK1 lead to Parkinson's disease. The study shows that PINK1 is imported into the translocase of the outer mitochondrial membrane (TOM) complex, leading to its activation by autophosphorylation and initiation of mitochondrial clearance. The crystal structures provide insights into the dimeric autophosphorylation complex and the stabilization mechanism of PINK1 on the core TOM complex.
Article
Clinical Neurology
Pin-Shiuan Chen, Ni-Chung Lee, Chieh-Ju Sung, Ya-Wen Liu, Wen-Chin Weng, Pi-Chuan Fan, Wang-Tso Lee, Yin-Hsiu Chien, Chao-Szu Wu, Yueh-Feng Sung, Ming-Chen Tsai, Yi-Chung Lee, Hsueh-Wen Hsueh, Sabrina Mai-Yi Fan, Meng-Chen Wu, Hsun Li, Huan-Yun Chen, Han- Lin, Chih-Hsin Ou-Yang, Wuh-Liang Hwuh, Chin-Hsien Lin
Summary: This study describes the clinical characteristics and functional findings in a cohort of patients with NDUFAF5 mutations, and reveals significant heterogeneity and divergent prognosis based on age at onset. This research is important for understanding the association between NDUFAF5 mutations and Leigh syndrome.
MOVEMENT DISORDERS
(2023)
Article
Immunology
Amir Arastehfar, Nevzat Unal, Tugrul Hosbul, Muhammed Alper Ozarslan, Ayse Sultan Karakoyun, Furkan Polat, Diego Fuentes, Ramazan Gumral, Tuba Turunc, Farnaz Daneshnia, David S. Perlin, Cornelia Lass-Florl, Toni Gabaldon, Macit Ilkit, M. Hong Nguyen
Summary: Critically ill COVID-19 patients in ICU have an elevated risk of candidemia, with prolonged ICU exposure and management as contributing factors. Improved infection control and antibiotic stewardship practices are necessary to reduce irrational antimicrobial utilization.
OPEN FORUM INFECTIOUS DISEASES
(2022)
Article
Sport Sciences
Alfredo Santalla, Pedro L. Valenzuela, Carlos Rodriguez-Lopez, Irene Rodriguez-Gomez, Gisela Nogales-Gadea, Tomas Pinos, Joaquin Arenas, Miguel A. Martin, Alejandro Santos-Lozano, MARiA Moran, Carmen Fiuza-Luces, Ignacio Ara, Alejandro Lucia
Summary: This study aimed to investigate the effects of a long-term exercise intervention on patients with McArdle disease. The results showed that a 2-year unsupervised exercise program was both safe and effective in improving the clinical course and aerobic fitness of these patients.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2022)
Article
Clinical Neurology
Maria Paz Guerrero-Molina, Montserrat Morales-Conejo, Aitor Delmiro, Maria Moran, Cristina Dominguez-Gonzalez, Elena Arranz-Canales, Ana Ramos-Gonzalez, Joaquin Arenas, Miguel A. Martin, Jesus Gonzalez de la Aleja
Summary: This study found that high-dose oral glutamine supplementation significantly reduces CSF glutamate and increases CSF glutamine levels in patients with MELAS syndrome. These findings may have potential therapeutic implications in these patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Guillermo Amate-Garcia, Maria Juliana Ballesta-Martinez, Pablo Serrano-Lorenzo, Rocio Garrido-Moraga, Adrian Gonzalez-Quintana, Alberto Blazquez, Juan C. Rubio, Ines Garcia-Consuegra, Joaquin Arenas, Cristina Ugalde, Maria Moran, Encarnacion Guillen-Navarro, Miguel A. Martin
Summary: We reported a neonatal patient with hypertrophic cardiomyopathy (HCM), lactic acidosis, and isolated complex I deficiency. Through molecular and functional assays, we identified a novel hemizygous variant in the NDUFB11 gene, which is associated with mitochondrial respiratory chain impairment. Our findings emphasize the importance of characterizing the molecular effect of new variants in the patient's tissues to demonstrate their pathogenicity and association with clinical phenotypes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Hrant Hovhannisyan, Antonio Rodriguez, Ester Saus, Mario Vaneechoutte, Toni Gabaldon
Summary: The study focuses on the challenges of analyzing transcriptomic interactions between host and pathogen RNA in in vivo conditions. The researchers successfully designed pan-Candida target capture probes to enrich protein-coding and non-coding transcriptomes in order to enhance transcriptomic analysis in four major Candida species. The probe-based enrichment approach showed better fidelity of expression levels, enabling species multiplexing and capturing of lncRNAs, and demonstrated robust genotype-based identification of the infecting strain present in the sample.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Ahmed Ibrahem Hafez, Beatriz Soriano, Aya Allah Elsayed, Ricardo Futami, Raquel Ceprian, Ricardo Ramos-Ruiz, Genis Martinez, Francisco Jose Roig, Miguel Angel Torres-Font, Fernando Naya-Catala, Josep Alvar Calduch-Giner, Lucia Trilla-Fuertes, Angelo Gamez-Pozo, Vicente Arnau, Jose Maria Sempere-Luna, Jaume Perez-Sanchez, Toni Gabaldon, Carlos Llorens
Summary: The GPRO suite is an ongoing bioinformatic project for the analysis of -omics data. It introduces a client- and server-side solution for comparative transcriptomics and variant analysis. The client-side includes two Java applications, RNASeq and VariantSeq, which manage pipelines and workflows using common command line tools. The server-side, named GPRO Server-Side, hosts all dependencies and requires a Linux operating system, PHP, SQL, Python, bash scripting, and third-party software. The solution offers both desktop and web applications, with step-by-step and pipeline modes for execution. It also features an experimental support system called GENIE, with a chatbot assistant and expert system for troubleshooting and recommendations.
Article
Oncology
Olfat Khannous-Lleiffe, Jesse R. Willis, Ester Saus, Victor Moreno, Sergi Castellvi-Bel, Toni Gabaldon
Summary: Colorectal cancer (CRC) is a global healthcare challenge influenced by genetic and environmental factors. This study used 16S rRNA sequencing to analyze FIT samples and found that the gut microbiome has predictive potential and undergoes changes during the progression from healthy tissue to carcinoma. These findings have implications for understanding the role of microbes in adenoma to carcinoma progression and improving CRC screening programs.
Article
Biology
Veronica Mixao, Juan Carlos Nunez-Rodriguez, Valentina del Olmo, Ewa Ksiezopolska, Ester Saus, Teun Boekhout, Attila Gacser, Toni Gabaldon
Summary: This study analyzed the genomic sequences of 55 hybrid strains of pathogenic yeast and found that genetic drift is the main force shaping LOH patterns in these genomes, and LOH patterns are likely the result of acute episodes rather than continuous accumulation of sporadic events.
Article
Biology
Irene Julca, Pablo Vargas, Toni Gabaldon
Summary: The evolutionary history of the Olea europaea complex involves hybridization and polyploidization events, leading to the formation of new subspecies. The genetic diversity of the species is crucial for its management and preservation of genetic resources.
Article
Biochemistry & Molecular Biology
Cho-Cho Aye, Dean E. Hammond, Sergio Rodriguez-Cuenca, Mary K. Doherty, Phillip D. Whitfield, Marie M. Phelan, Chenjing Yang, Rafael Perez-Perez, Xiaoxin Li, Angels Diaz-Ramos, Gopal Peddinti, Matej Oresic, Antonio Vidal-Puig, Antonio Zorzano, Cristina Ugalde, Silvia Mora
Summary: CBL is rapidly phosphorylated upon insulin receptor activation. Mice with whole body CBL depletion show improved insulin sensitivity and glucose clearance, but the precise mechanisms are unknown. Depletion of CBL or its associated protein SORBS1/CAP in myocytes leads to increased mitochondrial mass, greater proton leak, reduced activity and assembly of mitochondrial respiratory complex I, and alterations in proteins involved in glycolysis and fatty acid degradation. These findings demonstrate that the CBL/CAP pathway links insulin signaling to efficient mitochondrial function and metabolism in muscle.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Efe Aydin, Ester Saus, Uciel Chorostecki, Toni Gabaldon
Summary: Long noncoding RNAs (lncRNAs) have potential as prognostic biomarkers or therapeutic targets in cancer. Somatic mutations in lncRNAs have been associated with tumor relapse, but their underlying mechanisms are unknown. In this study, a recurrent A > G point mutation in NEAT1 was found to alter its structure and affect the binding of miRNAs. Differential expression analysis showed upregulation of Vimentin, consistent with previous findings. This study proposes a pipeline to explore the functional effects of lncRNA somatic mutations.
Article
Medicine, General & Internal
Laura Bermejo-Guerrero, Carlos Pablo de Fuenmayor-Fernandez de la Hoz, Maria Paz Guerrero-Molina, Paloma Martin-Jimenez, Alberto Blazquez, Pablo Serrano-Lorenzo, David Lora, Montserrat Morales-Conejo, Irene Gonzalez-Martinez, Elena Ana Lopez-Jimenez, Miguel A. Martin, Cristina Dominguez-Gonzalez
Summary: Primary mitochondrial myopathies (PMM) are a diverse group of diseases that can be easily confused with chronic fatigue syndrome (CFS). This study evaluated the potential of growth differentiation factor-15 (GDF-15) as a biomarker to differentiate PMM from CFS. The results showed that GDF-15 can accurately distinguish between PMM and CFS patients, making it a promising biomarker for further studies to exclude mitochondrial disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Pablo Serrano-Lorenzo, Dino Gobelli, Rocio Garrido-Moraga, Maria J. Esteban-Amo, Jose R. Lopez-Lopez, Antonio Orduna, Miguel A. de la Fuente, Miguel A. Martin, Maria Simarro
Summary: Increasing evidence shows that the electron transfer chain is crucial in controlling macrophages' effector functions. This study generated Ndufs4-/- mouse macrophage cell lines, which exhibit decreased complex I activity, altered complex I assembly, and reduced levels of maximal respiration and ATP production. These mitochondrial respiration alterations are associated with a pro-inflammatory cytokine profile response and enhanced phagocytosis of Gram-negative bacteria.
Article
Biochemical Research Methods
Laura D. T. Vo Ngoc, Randy Osei, Katrin Dohr, Catharina Olsen, Sara Seneca, Alexander Gheldof
Summary: EDIR is a database containing the positions of interspersed repeats within the human exome. It has been calculated using an inductive strategy and can be queried through an R/Bioconductor package or a web interface.
