Article
Endocrinology & Metabolism
Jay Kumar, Ghulam Mohammad, Kumari Alka, Renu A. Kowluru
Summary: Mitochondrial dysfunction plays a critical role in the development of diabetic retinopathy. Hyperglycemia downregulates the mtDNA-encoded LncRNA cytochrome B (LncCytB) in retinal endothelial cells, leading to impaired mtDNA packaging and increased vulnerability to damage.
Review
Biochemistry & Molecular Biology
Miroslava Stastna
Summary: The review focuses on proteomic approaches used to investigate qualitative/quantitative changes in mitochondrial proteins related to mitochondrial dysfunction and various pathologies. Proteomic techniques have become powerful tools for characterizing static and dynamic proteomes, detecting protein-protein interactions, and exploring post-translation modifications that are critical for mitochondrial regulation, maintenance, and function. The accumulated proteomic data can provide insights into disease prevention and treatment. This article also provides an overview of recent proteomic studies on the regulatory roles of post-translational modifications of mitochondrial proteins, specifically in cardiovascular diseases linked to mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Pallavi Shukla, Srabani Mukherjee, Anushree Patil, Beena Joshi
Summary: Emerging studies have found that mitochondrial dysfunction and mtDNA variants play a role in the development of PCOS. Rare variants in mtDNA, in addition to common variants, may modify the risk of disease. High throughput sequencing techniques allow for comprehensive characterization of mtDNA variants, but rare variants in mtDNA encoding genes have not been extensively explored in women with PCOS. This study analyzed mtDNA copy number and variants in mtDNA encoded genes in PCOS patients for the first time using NGS, and identified significant reduction in mtDNA copy number and numerous prioritized variants that may contribute to mitochondrial dysfunction in PCOS. This study provides novel insights into the pathogenesis of PCOS by focusing on mitochondrial genetic defects as an underlying cause of mitochondrial dysfunction in women with PCOS.
Review
Clinical Neurology
Sugumar Mani, Murugan Sevanan, Alagudurai Krishnamoorthy, Sathiya Sekar
Summary: Parkinson's disease is a chronic and progressive neurodegenerative disorder affecting approximately 1% of the global population. The etiology of PD is likely multifactorial, involving protein misfolding, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Mitochondrial dysfunction plays a key role in dopaminergic neuronal loss in PD, potentially leading to neuroinflammation and vice versa. Mitochondrial proteins are a promising target for PD development, but limited dopaminergic neurons hinder detailed investigation of mitochondrial dysfunction in PD.
NEUROLOGICAL SCIENCES
(2021)
Review
Cell Biology
Jannik Prasuhn, Ryan L. Davis, Kishore R. Kumar
Summary: Parkinson's disease is complicated and mitochondrial dysfunction plays a key role in its pathophysiology. While there are still gaps in knowledge, targeting various aspects of mitochondrial function and using combined therapeutic approaches may offer the best chance for developing effective novel therapies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Clinical Neurology
Amica C. Muller-Nedebock, Francois H. van Der Westhuizen, Sulev Koks, Soraya Bardien
Summary: Mitochondrial dysfunction plays a central role in Parkinson's disease pathogenesis, particularly affecting dopaminergic neurons. Variations and depletion of mtDNA in mitochondria can lead to inadequate energy production, contributing to the onset of disease phenotype. Studies suggest that nuclear-encoded genes associated with mtDNA processes may influence PD risk by disrupting mtDNA processes or impairing their regulation.
MOVEMENT DISORDERS
(2021)
Review
Biology
Luigi Del Giudice, Paola Pontieri, Mariarosaria Aletta, Matteo Calcagnile
Summary: Neurodegenerative diseases involve the progressive degeneration of nerve cells. Some of these diseases, such as Alzheimer's and Parkinson's, are caused by mitochondrial disorders. Mitochondria are organelles responsible for energy production and are influenced by both nuclear DNA and mitochondrial DNA. Recent research has identified three nuclear DNA genes that encode mitochondrial ribosomal proteins, which could be linked to neurodegenerative diseases. Understanding the role of these proteins could lead to potential therapeutic drugs. However, despite extensive research efforts, there is still no cure or effective treatment for neurodegenerative diseases.
Article
Multidisciplinary Sciences
Lei Tan, Xiaolong Qi, Weining Kong, Jiachuan Jin, Dan Lu, Xu Zhang, Yue Wang, Siting Wang, Wei Dong, Xudong Shi, Wei Chen, Jianying Wang, Keru Li, Yuan Xie, Lijuan Gao, Feifei Guan, Kai Gao, Chaojun Li, Cheng Wang, Zhibin Hu, Lianfeng Zhang, Xuejiang Guo, Bin Shen, Yuanwu Ma
Summary: We used a modified DddA-derived cytosine base editor to introduce premature stop codons in mitochondrial protein-coding genes, resulting in the depletion of mtProteins in both cell and rat resources. This provides valuable tools for studying mtProtein-coding genes and developing therapeutic strategies.
Review
Pharmacology & Pharmacy
Ting He, Xiaoyan Lin, Anping Su, Yujie Zhang, Zhichao Xing, Li Mi, Tao Wei, Zhihui Li, Wenshuang Wu
Summary: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, mainly affecting middle-aged and elderly individuals. This article presents a comprehensive search of recent publications exploring the potential of natural products in treating PD by restoring mitochondrial dysfunction. Multiple studies have demonstrated the beneficial effects of natural products in regulating mitochondrial dysfunction and potentially serving as therapeutic drugs for PD.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Pierpaolo Risiglione, Federica Zinghirino, Maria Carmela Di Rosa, Andrea Magri, Angela Messina
Summary: The function of alpha-Synuclein, its interaction with VDAC, and its involvement in pathological processes are the main focus of current research on mitochondrial function modulation.
Article
Neurosciences
Margalida Puigros, Anna Calderon, Alexandra Perez-Soriano, Cristina de Dios, Manel Fernandez, Anna Colell, Maria-Jose Marti, Eduardo Tolosa, Ramon Trullas
Summary: This study found differences in the content and deletion ratio of cf-mtDNA in the cerebrospinal fluid of patients with iPD and LRRK2-PD, suggesting different mitochondrial pathophysiology between these two forms of Parkinson's disease.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Margalida Puigr, Anna Calderon, Alexandra Perez-Soriano, Cristina de Dios, Manel Fernandez, Anna Colell, Maria-Jose Marti, Eduardo Tolosa, Ramon Trullas
Summary: Mitochondrial dysfunction occurs in both idiopathic (iPD) and LRRK2-related Parkinson's disease (LRRK2-PD), but previous studies have suggested different types of mitochondrial pathology in the two disorders. A novel multiplex digital PCR assay was developed to quantify cell-free mitochondrial DNA (cf-mtDNA) copy number and deletion ratio in cerebrospinal fluid (CSF). The results showed significant differences in cf-mtDNA content and deletion levels between iPD and LRRK2-PD, supporting the hypothesis of distinct mitochondrial pathophysiology in these diseases.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Avanti Gokhale, Chelsea E. Lee, Stephanie A. Zlatic, Amanda A. H. Freeman, Nicole Shearing, Cortnie Hartwig, Oluwaseun Ogunbona, Julia L. Bassell, Meghan E. Wynne, Erica Werner, Chongchong Xu, Zhexing Wen, Duc Duong, Nicholas T. Seyfried, Carrie E. Bearden, Viktor Janos Olah, Matthew J. M. Rowan, Jill R. Glausier, David A. Lewis, Victor Faundez
Summary: This study identified the importance of genes SLC25A1 and MRPL40, present in the deleted segment of 22q11.2 microdeletion syndrome, in maintaining mitochondrial ribosomal integrity and proteostasis, which are crucial for synaptic neurodevelopment and function. Fruit fly experiments demonstrated that mitochondrial ribosome function is essential for synaptic neurodevelopment, function, and behavior. Mitochondrial proteostasis perturbations, caused by genetic or environmental factors, may contribute to the pathogenesis of neurodevelopmental disorders.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Jia Liu, Jingjing Jiang, Jingru Qiu, Liyan Wang, Jing Zhuo, Baozhu Wang, Deqing Sun, Shuyan Yu, Haiyan Lou
Summary: UA, a gut metabolite produced from ellagic acid-containing foods, shows potential protective effects against PD by promoting mitochondrial biogenesis and preventing neurotoxicity induced by 6-OHDA. This study provides new insights into the role of UA in regulating mitochondrial dysfunction in PD and suggests potential therapeutic applications.
Article
Biochemistry & Molecular Biology
Carmina Warth Perez C. Arias, Ivan Silbern, Lucas Caldi Gomes, Hannes Wartmann, Vivian Dambeck, Jonas Fanz, Lisa Neuenroth, Mathias Baehr, Tiago F. Outeiro, Stefan Bonn, Christine Stadelmann-Nessler, Silvio O. Rizzoli, Christof Lenz, Henning Urlaub, Paul Lingor
Summary: Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. In this study, we analyzed PD-associated alterations in the hippocampus of PD patients and identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Our analysis suggests that NPTX1 contributes to synaptic pathology in late-stage PD and represents a putative target for novel therapeutic strategies.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yan S. Kim, Daria M. Potashnikova, Alisa M. Gisina, Irina Kholodenko, Arthur T. Kopylov, Olga Tikhonova, Leonid K. Kurbatov, Aleena A. Saidova, Anna Tvorogova, Roman Kholodenko, Pavel Belousov, Ivan A. Vorobjev, Victor G. Zgoda, Konstantin N. Yarygin, Alexey Yu Lupatov
Summary: CD133 plasma membrane expression is positively correlated with the proliferative activity of cancer cells. Transcriptomic and proteomic profiling revealed minor distinctions between different levels of CD133 expression. The TRIM28 transcription factor plays a prominent role in regulating CD133 expression. Knockout of the TRIM28 gene downregulates CD133 expression in Caco2 cell clones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marina Solovieva, Yuri Shatalin, Irina Odinokova, Olga Krestinina, Yulia Baburina, Yana Lomovskaya, Anton Pankratov, Natalia Pankratova, Olga Buneeva, Arthur Kopylov, Alexei Medvedev, Vladimir Akatov
Summary: DSF and its oxy-derivatives enhance the oxidation and ubiquitination of proteins, leading to inhibition of protein retrotranslocation and initiation of paraptosis-like cell death. This provides new insight into the role of protein ubiquitination/deubiquitination in regulating protein retrotranslocation and cell death.
Article
Biochemistry & Molecular Biology
Denis V. Petrovsky, Vladimir R. Rudnev, Kirill S. Nikolsky, Liudmila I. Kulikova, Kristina M. Malsagova, Arthur T. Kopylov, Anna L. Kaysheva
Summary: This article proposes a universal machine learning method called PSSNet for the recognition and segmentation of super-secondary structures (SSS). By utilizing the geometric features and primary sequences of SSS, this method can reliably select extensive SSS sets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Maxim S. Kondratyev, Vladimir R. Rudnev, Kirill S. Nikolsky, Denis V. Petrovsky, Liudmila I. Kulikova, Kristina A. Malsagova, Alexander A. Stepanov, Arthur T. Kopylov, Anna L. Kaysheva
Summary: This study aimed to investigate the potential interactions between the Anle138b isomer ligand and the intrinsically disordered alpha-synuclein protein. The results revealed the possibility of complex formation and identified the main types of interactions that stabilize the complex.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Arthur T. Kopylov, Alexander A. Stepanov, Tatiana V. Butkova, Kristina A. Malsagova, Natalia V. Zakharova, Georgy P. Kostyuk, Artem U. Elmuratov, Anna L. Kaysheva
Summary: This study utilized quantitative proteomic and metabolomic analysis, and GWAS genotyping to identify differently expressed proteins and metabolites in patients with schizophrenia. The integration of three omics layers proposed a map of molecular events associated with schizophrenia psychopathology.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Anna L. Kaysheva, Arthur T. Kopylov, Alexander A. Stepanov, Kristina A. Malsagova, Alexander A. Izotov, Yevgeniya I. Shurubor, Boris F. Krasnikov
Summary: A highly sensitive method for the qualitative and quantitative determination of amino- and carboxylic acids, as well as a number of urea and methionine cycle metabolites in the studied solutions, is presented. Derivatives were obtained for amino and carboxylic acids through specific reactions. The developed methods and obtained experimental data are of interest for a wide range of biomedical studies and monitoring the content of endogenous metabolites in biological samples under various pathological conditions.
Article
Sport Sciences
Denis Petrovsky, Vasiliy Pustovoyt, Kirill S. Nikolsky, Kristina A. Malsagova, Arthur T. Kopylov, Alexander A. Stepanov, Vladimir R. Rudnev, Evgenii Balakin, Anna L. Kaysheva
Summary: This study analyzed the health indicators of athletes during training and competitive periods and identified the most significant indicators related to catabolism and anabolism phenotypes using machine learning methods. Parameters of muscle metabolism and the ornithine cycle contributed significantly to the classification of metabolism types.
Article
Sport Sciences
Kristina A. Malsagova, Arthur T. Kopylov, Alexander A. Stepanov, Dmitry V. Enikeev, Natalia V. Potoldykova, Evgenii I. Balakin, Vasiliy I. Pustovoyt, Anna L. Kaysheva
Summary: The aim of this study was to investigate the effects of high-intensity training under extreme conditions on the metabolism and immunological reactions of athletes. Blood samples were collected from male triathletes before and after exercise, and metabolomic analysis identified changes in metabolites and hormones. It was found that exercise led to changes in the intermediate products of tricarboxylic and amino acids. The study highlights the importance of monitoring athletes' biochemical parameters and analyzing their eating behavior to identify individual deficiencies and react timely.
Review
Biochemistry & Molecular Biology
Olga A. Buneeva, Arthur T. Kopylov, Alexei E. Medvedev
Summary: Proteasomes are crucial in the degradation of short-lived, regulatory, misfolded, and damaged proteins, and their dysfunction is associated with neurodegenerative diseases. Proteasome-associated proteins play important roles in proteasome functioning, accounting for at least 28% of the human brain proteome. The proteasome interactome in the brain involves proteins involved in complex assembly, regulation, and localization, and these interactions are crucial for nucleotide-dependent functions of proteasomes.
BIOCHEMISTRY-MOSCOW
(2023)
Article
Biochemistry & Molecular Biology
Olga Buneeva, Arthur Kopylov, Oksana Gnedenko, Marina Medvedeva, Alexander Veselovsky, Alexis Ivanov, Victor Zgoda, Alexei Medvedev
Summary: Affinity-based proteomic profiling is used to identify proteins involved in interactomes. In this study, affinity-based separation of mouse brain proteins combined with mass spectrometry identification was used to evaluate protein partners bound to PKM1. The identified proteins were validated by quantitative affinity binding using a surface plasmon resonance biosensor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Alexander A. Stepanov, Kristina A. Malsagova, Arthur T. Kopylov, Vladimir R. Rudnev, Dmitry E. Karateev, Evgenia I. Markelova, Elena L. Luchikhina, Elena E. Borisova, Anna L. Kaysheva
Summary: A reduction in the activities of tumor necrosis factor (TNFα) and interleukin-6 (IL-6) is an effective strategy for treating rheumatoid arthritis (RA). However, the mechanisms and outcomes of two different therapies targeting these cytokines are still not well understood. This comparative longitudinal study aimed to investigate the metabolic and proteomic differences in patients treated with anti-TNF or anti-IL-6 strategies.
Article
Biochemistry & Molecular Biology
Denis V. Petrovskiy, Kirill S. Nikolsky, Vladimir R. Rudnev, Liudmila I. Kulikova, Tatiana V. Butkova, Kristina A. Malsagova, Arthur T. Kopylov, Anna L. Kaysheva
Summary: This article introduces a new tool called SAFoldNet, which uses neural networks to search and align protein structures. The study shows that this method is competitive in searching and aligning protein structures, and a user-friendly web interface service has been developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Denis V. Petrovskiy, Kirill S. Nikolsky, Vladimir R. Rudnev, Liudmila I. Kulikova, Tatiana V. Butkova, Kristina A. Malsagova, Arthur T. Kopylov, Anna L. Kaysheva
Summary: This paper discusses the impact of post-translational modifications and amino acid substitutions on the 3D structure of proteins and focuses on predicting accurate PTMs in proteins. The study also compares algorithmic solutions with existing structure modeling packages and explores their potential for further development and optimization.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Kirill Sergeevich Nikolsky, Liudmila Ivanovna Kulikova, Denis Vitalievich Petrovskiy, Vladimir Removich Rudnev, Tatiana Vladimirovna Butkova, Kristina Akhmedovna Malsagova, Arthur Tigranovich Kopylov, Anna Leonidovna Kaysheva
Summary: In this study, we investigated the autonomous stability of three-helix bundle and SH3-type barrels outside the protein environment. Through molecular experiments and comparative analysis, we demonstrated the potential for reducing computational time and improving performance without significant loss of information.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Alexander Stepanov, Svetlana A. A. Usharova, Kristina A. A. Malsagova, Larisa K. K. Moshetova, Ksenia I. I. Turkina, Arthur T. T. Kopylov, Anna L. L. Kaysheva
Summary: Proteomic analysis of tear samples revealed a large proportion of shared proteins between central retinal vein occlusion (CRVO) patients and healthy volunteers. Comparative analysis identified 29 significantly different proteins between the groups, and a map of CRVO-related critical protein interactions was customized. The analysis highlighted inflammation, impairment of retinal hemostasis, and immune response as the main processes associated with CRVO ischemic condition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)