Article
Biochemistry & Molecular Biology
Qinghuan Kong, Xiaoyu Yan, Meiyu Cheng, Xin Jiang, Long Xu, Luyan Shen, Huimei Yu, Liankun Sun
Summary: In ovarian cancer cells, p62 coordinates the mitochondrial localization of p53, promoting cell apoptosis by inhibiting mtDNA transcription and mitochondrial function, leading to enhanced sensitivity to cisplatin.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Multidisciplinary Sciences
Min Ji Yoon, Boyoon Choi, Eun Jin Kim, Jiyeon Ohk, Chansik Yang, Yeon-Gil Choi, Jinyoung Lee, Chanhee Kang, Hyun Kyu Song, Yoon Ki Kim, Jae-Sung Woo, Yongcheol Cho, Eui-Ju Choi, Hosung Jung, Chungho Kim
Summary: The study reveals that UXT functions as an autophagy adaptor for p62-dependent aggrephagy, delaying motor neuron degeneration in a Xenopus model. Additionally, the cooperative relationship between molecular chaperones and the aggrephagy machinery is demonstrated for efficient removal of misfolded protein aggregates.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Jiafeng Chen, Zheng Gao, Xiaogang Li, Yinghong Shi, Zheng Tang, Weiren Liu, Xin Zhang, Ao Huang, Xuanming Luo, Qiang Gao, Guangyu Ding, Kang Song, Jian Zhou, Jia Fan, Xiutao Fu, Zhenbin Ding
Summary: The study indicates that abundant expression of p62 is associated with the malignant progression of ICC and could serve as a potential therapeutic target in antimetastatic strategies.
Article
Biochemistry & Molecular Biology
Sara Cazzaro, Xingyu Zhao, Victoria K. Zhao, Yenna K. Kim, Jung-A A. Woo
Summary: Accumulation of toxic protein assemblies and dysfunctional mitochondria are major contributors to the progression of Alzheimer's disease (AD). This study investigates the role of SSH1 in regulating mitochondrial health, respiration, and clearance of damaged mitochondria, as well as its impact on synaptic integrity. The results indicate that SSH1 negatively influences mitochondria through the cofilin-binding N-terminal region and impairs mitophagy through a p62-binding domain in the C-terminal region, making it a potential target for AD therapeutics.
HUMAN MOLECULAR GENETICS
(2023)
Article
Cell Biology
Heide Schatten
Summary: Selective autophagy is a targeted degradation process that eliminates specific intracellular substrates through the autophagy pathway. Blocking autophagy in cumulus granulosa cells directly affects citrate levels and thus affects oocyte maturation quality. The connection between SQSTM1 and K63-polyubiquitinated ACLY compromises citrate homeostasis and can be used as an indicator of oocyte meiotic maturation quality in cumulus granulosa cells.
Article
Cell Biology
Joo-Hui Han, Keun-Woo Jang, Chang-Seon Myung
Summary: Garcinia cambogia attenuates the expression of CEBPB, a key factor in adipogenesis, and inhibits autophagic flux, potentially providing new therapeutic targets for the treatment of obesity.
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
Cell Biology
Meiting Li, Jiannan Xiong, Liqian Yang, Jie Huang, Yu Zhang, Minghui Liu, Lina Wang, Jianguo Ji, Ying Zhao, Wei-Guo Zhu, Jianyuan Luo, Haiying Wang
Summary: The study reveals a new function of p62 in base excision repair, distinct from its known functions. Loss of p62 impairs repair capacity and increases cancer cell sensitivity to alkylating and oxidizing agents. Therefore, targeting p62 may have potential for cancer therapeutics.
Article
Multidisciplinary Sciences
Jiajun Zhu, Simon Schworer, Mirela Berisa, Yeon Ju Kyung, Keun Woo Ryu, Junmei Yi, Xuejun Jiang, Justin R. Cross, Craig B. Thompson
Summary: NADK2 is crucial for mitochondrial NADP(H) generation, which is essential for cell proliferation and proline biosynthesis. Its deletion can impact cell growth.
Article
Genetics & Heredity
Dong Li, Michael E. March, Paola Fortugno, Liza L. Cox, Leticia S. Matsuoka, Rosanna Monetta, Christoph Seiler, Louise C. Pyle, Emma C. Bedoukian, Maria Jose Sanchez-Soler, Oana Caluseriu, Katheryn Grand, Allison Tam, Alicia R. P. Aycinena, Letizia Camerota, Yiran Guo, Patrick Sleiman, Bert Callewaert, Candy Kumps, Annelies Dheedene, Michael Buckley, Edwin P. Kirk, Anne Turner, Benjamin Kamien, Chirag Patel, Meredith Wilson, Tony Roscioli, John Christodoulou, Timothy C. Cox, Elaine H. Zackai, Francesco Brancati, Hakon Hakonarson, Elizabeth J. Bhoj
Summary: Teebi hypertelorism syndrome (THS) is a rare craniofacial disorder caused by CDH11 variants, resulting in features such as hypertelorism, prominent forehead, and short nose. Heterozygous CDH11 variants decrease cell-cell adhesion and increase cell migratory behavior, leading to a form of THS known as CDH11-related THS.
Article
Biology
Kelsey A. Nolden, John M. Egner, Jack J. Collier, Oliver M. Russell, Charlotte L. Alston, Megan C. Harwig, Michael E. Widlansky, Souphatta Sasorith, Ines A. Barbosa, Andrew Gl Douglas, Julia Baptista, Mark Walker, Deirdre E. Donnelly, Andrew A. Morris, Hui Jeen Tan, Manju A. Kurian, Kathleen Gorman, Santosh Mordekar, Charu Deshpande, Rajib Samanta, Robert McFarland, R. Blake Hill, Robert W. Taylor, Monika Olahova
Summary: Imbalances in mitochondrial and peroxisomal dynamics contribute to human neurological disorders. This study focused on the role of DRP1 variants in these disorders, revealing that mutations affecting different DRP1 domains lead to developmental delay, seizures, hypotonia, and cardiac complications. The severity of clinical phenotypes correlated with specific variants, with stalk domain variants resulting in more severe symptoms. These mutations impaired protein oligomerisation, DRP1-peroxisomal recruitment, and mitochondrial and peroxisomal hyperfusion. The study also identified a novel pathogenic mechanism, where a specific variant uncouples DRP1 assembly from GTP hydrolysis.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Huifang Liu, Philip Wing-Lok Ho, Chi-Ting Leung, Shirley Yin-Yu Pang, Eunice Eun Seo Chang, Zoe Yuen-Kiu Choi, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Summary: Mitochondrial dysfunction and clearance of defective mitochondria are associated with LRRK2 mutation in aging brain, leading to Parkinson disease pathogenesis.
Article
Endocrinology & Metabolism
Shenghui Chen, Xinyu Wang, Zhening Liu, Jinghua Wang, Yanjun Guo, Qinqiu Wang, Hangkai Huang, Youming Li, Chaohui Yu, Chengfu Xu
Summary: OLFM4 is significantly upregulated in patients with NAFLD and in cellular and mouse models of NAFLD. OLFM4 deficiency exacerbates diet-induced hepatic steatosis and inflammation through P62-dependent mitophagy. Blocking the P62-ZZ-domain prevents diet-induced NAFLD in OLFM4 deficient mice.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Article
Cell & Tissue Engineering
Boer Li, Yu Shi, Mengyu Liu, Fanzi Wu, Xuchen Hu, Fanyuan Yu, Chenglin Wang, Ling Ye
Summary: The study found that NAD(+)-mediated mitochondrial OXPHOS is essential for osteogenic commitment in BMSCs and bone repair, which may provide a potential therapeutic target for bone repair and regeneration.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Clinical Neurology
Susana Lopez-Ortiz, Simone Lista, Pedro L. Valenzuela, Jose Pinto-Fraga, Ricardo Carmona, Filippo Caraci, Giuseppe Caruso, Nicola Toschi, Enzo Emanuele, Audrey Gabelle, Robert Nistico, Francesco Garaci, Alejandro Lucia, Alejandro Santos-Lozano
Summary: The study summarizes the relationship between physical activity and the development of Alzheimer's disease, as well as the impact of exercise on patients with Alzheimer's disease. The findings suggest that physical activity can lower the risk of Alzheimer's disease and exercise has positive effects on cognitive function, physical performance, and functional independence.
JOURNAL OF NEUROLOGY
(2023)
Article
Geriatrics & Gerontology
Lisa Perus, Jean-Francois Mangin, Jeremy Deverdun, Laure-Anne Gutierrez, Emmanuelle Gourieux, Clara Fischer, Liesjet E. H. Van Dokkum, Clara Manesco, Germain Busto, Sophie Guyonnet, Bruno Vellas, Audrey Gabelle, Emmanuelle Le Bars
Summary: This study aims to explore the impact of multi-domain preventive interventions on older adults, especially those at higher risk of developing Alzheimer's disease (AD). The results indicate that such interventions have a certain effect on changes in brain functional connectivity, especially in frontoparietal, salience, visual, and sensorimotor networks in individuals with cognitive decline. These findings are independent of cortical thickness and vascular burden.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Letter
Clinical Neurology
Sylvain Lehmann, Susanna Schraen-Maschke, Jean-Sebastien Vidal, Bernadette Allinquant, Stephanie Bombois, Audrey Gabelle, Olivier Hanon
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Andrey Y. Y. Vinokurov, Vladislav O. O. Soldatov, Evgenia S. S. Seregina, Angelina I. I. Dolgikh, Pavel A. A. Tagunov, Andrey V. V. Dunaev, Marina Y. Y. Skorkina, Alexey V. V. Deykin, Andrey Y. Y. Abramov
Summary: Alterations in function of HPRT lead to overproduction of uric acid and symptoms of LNS. HPRT1 deficiency inhibits mitochondrial respiration and increases ROS production, but does not induce oxidative stress or decrease the level of antioxidant glutathione.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Clinical Neurology
Christophe Hirtz, Germain U. Busto, Karim Bennys, Jana Kindermans, Sophie Navucet, Laurent Tiers, Simone Lista, Jerome Vialaret, Laure-Anne Gutierrez, Yves Dauvilliers, Claudine Berr, Sylvain Lehmann, Audrey Gabelle
Summary: Blood plasma biomarkers, especially the IPMS-Shim technology, have potential value as a screening tool for early AD patients.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Noemi Esteras, Thomas S. Blacker, Evgeny A. Zherebtsov, Olga A. Stelmashuk, Ying Zhang, W. Christian Wigley, Michael R. Duchen, Albena T. Dinkova-Kostova, Andrey Y. Abramov
Summary: The transcription factor Nrf2 and its repressor Keap1 play a crucial role in cell stress adaptation by regulating gene expression related to cellular detoxification, antioxidant defense, and energy metabolism. This study investigated the impact of Nrf2 on glucose distribution and the connection between NADH production in energy metabolism and NADPH homeostasis using glio-neuronal cultures. The findings showed that Nrf2 activation enhances glucose uptake in neurons and astrocytes, with prioritized consumption for mitochondria-related energy production rather than NADPH synthesis in the pentose phosphate pathway.
Article
Biochemistry & Molecular Biology
Plamena R. Angelova, Isabella Myers, Andrey Y. Abramov
Summary: A study found that carbon monoxide (CO) poisoning is a major cause of toxic mortality and morbidity. Reactive oxygen species were found to be generated in response to toxic doses of CO exposure, leading to lipid peroxidation and a decrease in GSH. Inhibition of different phases of reactive oxygen species generation protected cells against CO-induced oxidative stress and cell death, with the most significant effect observed during NADPH oxidase inhibition.
Correction
Neurosciences
Regina H. Reynolds, Aaron Z. Wagen, Frida Lona-Durazo, Sonja W. Scholz, Maryam Shoai, John Hardy, Sarah A. Gagliano Taliun, Mina Ryten
NPJ PARKINSONS DISEASE
(2023)
Article
Multidisciplinary Sciences
Karishma D'Sa, Sebastian Guelfi, Jana Vandrovcova, Regina H. Reynolds, David Zhang, John Hardy, Juan A. Botia, Michael E. Weale, Sarah A. Gagliano Taliun, Kerrin S. Small, Mina Ryten
Summary: This study revealed that the genetic regulation of gene expression mainly occurs post-transcriptionally in the cytoplasm, with synaptic genes more likely to undergo this form of regulation. These findings are crucial for understanding the structure of gene expression regulation in the human brain and interpreting large-scale gene association studies.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Benjamin O'Callaghan, John Hardy, Helene Plun-Favreau
Summary: The genetics of Parkinson's disease has played a crucial role in understanding the PINK1-dependent mitophagy process. In this article, we examine the implications of a 2010 PLOS Biology paper that provided insight into the functional significance of PINK1 in the mitophagy cascade.
Article
Genetics & Heredity
Nurlan Kerimov, Ralf Tambets, James D. Hayhurst, Ida Rahu, Peep Kolberg, Uku Raudvere, Ivan Kuzmin, Anshika Chowdhary, Andreas Vija, Hans J. Teras, Masahiro Kanai, Jacob Ulirsch, Mina Ryten, John Hardy, Sebastian Guelfi, Daniah Trabzuni, Sarah Kim-Hellmuth, William Rayner, Hilary Finucane, Hedi Peterson, Abayomi Mosaku, Helen Parkinson, Kaur Alasoo
Summary: The eQTL Catalogue is an open database of uniformly processed human molecular quantitative trait loci (QTLs) that has been continuously updated to improve its utility in interpreting genetic associations with complex traits. The updates include an increase in the number of studies and datasets covered, implementation of statistical fine mapping, and development of static QTL coverage plots. These updates have been demonstrated to be useful in interpreting genetic variants associated with vitamin D levels in human plasma and will facilitate the interpretation of complex trait associations identified by other human genetics efforts.
Letter
Clinical Neurology
John Hardy
BRAIN COMMUNICATIONS
(2023)
Article
Clinical Neurology
Connor Langworth-Green, Saisha Patel, Zane Jaunmuktane, Edwin Jabbari, Huw Morris, Maria Thom, Andrew Lees, John Hardy, Michael Zandi, Karen Duff
Summary: Tauopathies are neurodegenerative disorders characterized by the aggregation of tau protein. Chronic inflammation plays a significant role in the pathogenesis of Alzheimer's disease, but its effects on tau pathology have been overlooked. Factors such as infection, brain injury, seizures, and autoimmune disease can trigger tau pathology through inflammatory processes. Understanding the chronic effects of inflammation on tauopathies may lead to the development of immunomodulatory interventions for clinical use.
Article
Medicine, Research & Experimental
Xiaopu Zhou, Yu Chen, Fanny C. F. Ip, Yuanbing Jiang, Han Cao, Ge Lv, Huan Zhong, Jiahang Chen, Tao Ye, Yuewen Chen, Yulin Zhang, Shuangshuang Ma, Ronnie M. N. Lo, Estella P. S. Tong, Vincent C. T. Mok, Timothy C. Y. Kwok, Qihao Guo, Kin Y. Mok, Maryam Shoai, John Hardy, Lei Chen, Amy K. Y. Fu, Nancy Y. Ip
Summary: Zhou et al. utilize deep learning to improve polygenic risk analysis for Alzheimer's disease. Their computational approach outperforms existing statistical methods and helps to identify potential biological mechanisms of Alzheimer's disease risk.
COMMUNICATIONS MEDICINE
(2023)
Article
Cell Biology
Karri Kaivola, Ruth Chia, Jinhui Ding, Memoona Rasheed, Masashi Fujita, Vilas Menon, Ronald L. Walton, Ryan L. Collins, Kimberley Billingsley, Harrison Brand, Michael Talkowski, Xuefang Zhao, Ramita Dewan, Ali Stark, Anindita Ray, Sultana Solaiman, Pilar Alvarez Jerez, Laksh Malik, Ted M. Dawson, Liana S. Rosenthal, Marilyn S. Albert, Olga Pletnikova, Juan C. Troncoso, Mario Maselis, Julia Keith, Eric Int LBD Genomics Consortium, Ali Int ALS FTD Consortium, Pentti PROSPECT Consortium, Toshiko Tanaka, Eric Topol, Ali Torkamani, Pentti Tienari, Tatiana M. Foroud, Bernardino Ghetti, John E. Landers, Mina Rtyen, Huw R. Morris, John A. Hardy, Letizia Mazzini, Sandra D'Alfonso, Cristina Moglia, Andrea Calvo, Geidy E. Serrano, Thomas G. Beach, Tanis Ferman, Neill R. Graff-Radford, Bradley F. Boeve, Zbigniew K. Wszolek, Dennis W. Dickson, Adriano Chio, David A. Bennett, Philip L. De Jager, Owen A. Ross, Clifton L. Dalgard, J. Raphael Gibbs, Bryan J. Traynor, Sonja W. Scholz
Summary: This study characterized the role of structural variants in Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). The researchers discovered a novel risk locus for LBD and found associations between known structural variants and FTD/ALS. Rare pathogenic structural variants were also identified in both LBD and FTD/ALS. The study provides a catalog of structural variants for further understanding of the pathogenesis of these forms of dementia.