Article
Microbiology
Youbao Zhao, Xiaorong Lin
Summary: The transcription factor Pas2 was found to be a key regulator in metabolic response to hypoxia in the human fungal pathogen Cryptococcus neoformans, interacting with another transcription factor Rds2. The Pas2/Rds2 complex plays a critical role in rewiring metabolism between respiration and fermentation, shedding light on the adaptation mechanisms of lower eukaryotes like C. neoformans to low oxygen levels.
Review
Biochemistry & Molecular Biology
Bo-Kun Yin, Zhao-Qi Wang
Summary: Members of the PIKK family, including TRRAP, are crucial in various biological processes such as DNA damage response and transcription. TRRAP, despite lacking enzymatic activity, acts as an adapter protein and scaffold protein in regulating cell functions and gene transcription, particularly in neural homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Jian-Xian Lin, Ning-Zi Lian, You-Xin Gao, Qiao-Ling Zheng, Ying-Hong Yang, Yu-Bin Ma, Zhi-Song Xiu, Qing-Zhu Qiu, Hua-Gen Wang, Chao-Hui Zheng, Ping Li, Jian-Wei Xie, Jun Lu, Qi-Yue Chen, Long-Long Cao, Mi Lin, Jia-Bin Wang, Chang-Ming Huang
Summary: LHPP expression is significantly decreased in gastric cancer tissues and is associated with poor prognosis and chemotherapy sensitivity. The study also found that LHPP is regulated by m6A methylation and regulates the metabolism of gastric cancer by changing the acetylation level. These findings suggest that LHPP may serve as a potential predictive biomarker and therapeutic target for gastric cancer.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Xiaojun Li, Linya Yao, Tao Wang, Xiaolei Gu, Yufan Wu, Ting Jiang
Summary: Overexpressed POLRMT is associated with the development and poor survival of prostate cancer. Depletion of POLRMT impairs mitochondrial functions and induces oxidative stress and apoptosis in prostate cancer cells. Moreover, overexpression of POLRMT enhances the proliferation and migration of prostate cancer cells.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Donatienne D'Hose, Lionel Mignion, Loic Hamelin, Pierre Sonveaux, Benedicte F. Jordan, Bernard Gallez
Summary: This study found that statins could decrease the oxygen consumption rate and increase mitochondrial superoxide production in cancer cells. In a mouse model, statins were able to improve tumor oxygenation, but had limited impact on tumor growth and radiosensitivity.
Article
Cell Biology
Yu Wu, Xinyou Lv, Haiting Wang, Kai Qian, Jinjun Ding, Jiejie Wang, Shushan Hua, Tiancheng Sun, Yiting Zhou, Lina Yu, Shuang Qiu
Summary: Neuronal activity induces retrograde translocation and nuclear accumulation of endosomal adaptor APPL1, which is necessary for the regulation of gene transcription and maintenance of hippocampal late-phase long-term potentiation. These results illustrate an APPL1-mediated pathway that contributes to the modulation of synaptic plasticity via coupling neuronal activity with chromatin remodeling.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Article
Cell Biology
Maristella Canovai, Monica Evangelista, Alberto Mercatanti, Romina D'Aurizio, Letizia Pitto, Francesca Marrocolo, Valentina Casieri, Marco Pellegrini, Vincenzo Lionetti, Sergio Bracarda, Milena Rizzo
Summary: In this study, we found that miR-96-5p, miR-183-5p, and miR-210-3p released by DCT resistant PCa clones decrease the efficacy of DCT in PCa cells. These miRNAs were found to interact with genes including FOXO1, IGFBP3, PDCD4, PPP2CB, and INSIG1, affecting the sensitivity of DCT. Additionally, circulating miR-183-5p and miR-21-5p were identified as potential biomarkers for predicting DCT resistance in PCa patients.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Rebecca L. Westbrook, Esther Bridges, Jennie Roberts, Cristina Escribano-Gonzalez, Katherine L. Eales, Lisa A. Vettore, Paul D. Walker, Elias Vera-Siguenza, Himani Rana, Federica Cuozzo, Kattri-Liis Eskla, Hans Vellama, Abeer Shaaban, Colin Nixon, Hendrik Luuk, Gareth G. Lavery, David J. Hodson, Adrian L. Harris, Daniel A. Tennant
Summary: Insufficient oxygen supply in the tumor microenvironment leads to difficulties in cancer cell proliferation. The increased activity of mitochondrial enzyme PYCR1 under hypoxic conditions is crucial for maintaining TCA cycle activity and preventing widespread cell death.
Article
Multidisciplinary Sciences
Nikita Sushentsev, Mary A. McLean, Anne Y. Warren, Arnold J. Benjamin, Cara Brodie, Amy Frary, Andrew B. Gill, Julia Jones, Joshua D. Kaggie, Benjamin W. Lamb, Matthew J. Locke, Jodi L. Miller, Ian G. Mills, Andrew N. Priest, Fraser J. L. Robb, Nimish Shah, Rolf S. Schulte, Martin J. Graves, Vincent J. Gnanapragasam, Kevin M. Brindle, Tristan Barrett, Ferdia A. Gallagher
Summary: Hyperpolarised C-13-MRI is a clinical technique that can differentiate clinically significant prostate cancer from indolent disease by measuring metabolic differences in the epithelial and stromal compartments of the tumor.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Wei Gong, Jiancheng Xu, Yan Wang, Qingjie Min, Xu Chen, Weimin Zhang, Jie Chen, Qimin Zhan
Summary: CircPUM1 plays a critical role in the stability of mitochondrial complex III and ATP production in ESCC cells. Its expression level is correlated with HIF1 alpha accumulation and it acts as a scaffold for interactions between UQCRC1 and UQCRC2.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Review
Cell Biology
Lara Bideyan, Rohith Nagari, Peter Tontonoz
Summary: This passage discusses the complex changes in hepatic gene expression in mammals during fasting and feeding transitions, highlighting the factors influencing these changes and the regulatory effects of dietary modifications on hepatic gene expression programs.
GENES & DEVELOPMENT
(2021)
Article
Gastroenterology & Hepatology
Peter A. C. Wing, Peter Jianrui Liu, James M. Harris, Andrea Magri, Thomas Michler, Xiaodong Zhuang, Helene Borrmann, Rosalba Minisini, Nicholas R. Frampton, Jochen M. Wettengel, Laurent Mailly, Valentina D'Arienzo, Tobias Riedl, Luis Nobre, Michael P. Weekes, Mario Pirisi, Mathias Heikenwalder, Thomas F. Baumert, Ester M. Hammond, David R. Mole, Ulrike Protzer, Peter Balfe, Jane A. McKeating
Summary: HIFs play a crucial role in regulating HBV replication, revealing an evolutionary mechanism by which HBV exploits the HIF signaling pathway to persist in the low oxygen environment of the liver.
JOURNAL OF HEPATOLOGY
(2021)
Article
Chemistry, Medicinal
David C. McKinney, Brian J. McMillan, Matthew Ranaghan, Jamie A. Moroco, Merissa Brousseau, Zachary Mullin-Bernstein, Meghan O'Keefe, Patrick McCarren, Michael F. Mesleh, Kathleen M. Mulvaney, Foxy Robinson, Ritu Singh, Besnik Bajrami, Florence F. Wagner, Robert Hilgraf, Martin J. Drysdale, Arthur J. Campbell, Adam Skepner, David E. Timm, Dale Porter, Virendar K. Kaushik, William R. Sellers, Alessandra Ianari
Summary: PRMT5 and its substrate adaptor proteins are essential for methylation of various substrates, including histones and spliceosome complexes. A compound series has been developed that can disrupt PRMT5-Riok1 complexes by binding to the PRMT5-PBM interface, providing a potential new approach for developing selective PRMT5 inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Laura Puente-Santamaria, Lucia Sanchez-Gonzalez, Nuria Pescador, Oscar Martinez-Costa, Ricardo Ramos-Ruiz, Luis del Peso
Summary: This study utilized meta-analysis techniques to integrate multiple transcription datasets from different experimental conditions, revealing the impact of hypoxia on gene expression and identifying a set of robust hypoxia-regulated gene signatures.
Article
Biochemistry & Molecular Biology
Mengmeng Liu, Janusz J. J. Zwiazek
Summary: This study investigated the physiological and transcriptional changes induced by root hypoxia in the distal parts of roots in canola plants. The plants responded to hypoxia by reducing growth and gas exchange rates, as well as decreasing leaf water potential and root hydraulic conductivity. Increased deposition of lignin and suberin was observed in the root tissues of hypoxic plants. The transcriptomic data revealed significant changes in gene expression in response to hypoxia, including the upregulation of BnPIP1;3, which may play an important role in hypoxia tolerance. The study also identified rearrangements in signaling pathways and transcription factors associated with the regulation of various genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Angela Riedel, Moutaz Helal, Luisa Pedro, Jonathan J. Swietlik, David Shorthouse, Werner Schmitz, Lisa Haas, Timothy Young, Ana S. H. da Costa, Sarah Davidson, Pranjali Bhandare, Elmar Wolf, Benjamin A. Hall, Christian Frezza, Thordur Oskarsson, Jacqueline D. Shields
Summary: Communication between tumors and tumor-draining lymph nodes alters the structure and function of the lymph nodes before metastasis. Tumor-derived lactic acid modulates the function of lymph node fibroblasts, resembling activated fibroblasts, and alters mitochondrial function. The role of lymph nodes in supporting cancer metastasis remains unclear.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Cell Biology
Rebecca Harris, Ming Yang, Christina Schmidt, Chloe Royet, Sarbjit Singh, Amarnath Natarajan, May Morris, Christian Frezza, Heike Laman
Summary: Fbxo7 plays a crucial role in cancer and Parkinson's disease by promoting Cdk6 activation and regulating the ubiquitination and phosphorylation of PFKP. Cells lacking Fbxo7 show reduced Cdk6 activity, and hematopoietic and lymphocytic cells are highly dependent on Fbxo7. Decreased Fbxo7 expression in T cells leads to increased glycolysis, but lower cell viability and activation levels.
JOURNAL OF CELL BIOLOGY
(2022)
Correction
Cell Biology
Cholsoon Jang, Sheng Hui, Xianfeng Zeng, Alexis J. Cowan, Lin Wang, Li Chen, Raphael J. Morscher, Jorge Reyes, Christian Frezza, Ho Young Hwang, Akito Imai, Yoshiaki Saito, Keitaro Okamoto, Christine Vaspoli, Loewe Kasprenski, Gerald A. Zsido, Joseph H. Gorman, Robert C. Gorman, Joshua D. Rabinowitz
Article
Biochemistry & Molecular Biology
Fay M. Allen, Ana S. H. Costa, Anja Gruszczyk, Georgina R. Bates, Hiran A. Prag, Efterpi Nikitopoulou, Carlo Viscomi, Christian Frezza, Andrew M. James, Michael P. Murphy
Summary: The study developed a rapid fractionation procedure to stabilize the distribution of metabolites between mitochondria and the cytosol. The procedure revealed the compartmentation of mitochondrial metabolites in vivo and allows for the assessment of metabolite distribution between the cytosol and mitochondria in various situations.
Review
Biochemistry & Molecular Biology
Grace Kennedy, Olivia Gibson, Daire T. O'Hare, Ian G. Mills, Emma Evergren
Summary: Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a serine/threonine protein kinase involved in regulating energy homeostasis and cell growth. Its deregulation has implications in metabolic diseases and cancer. Recent research has explored new functions of CaMKK2, such as lipogenesis and Golgi vesicle trafficking. This review discusses the role of CaMKK2 in membrane trafficking mechanisms and its implications for disease.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Patricia Sanchez-Perez, Ana Mata, May-Kristin Torp, Elia Lopez-Bernardo, Christina M. Heiestad, Jan M. Aronsen, Antonio Molina-Iracheta, Luis Jesus Jimenez-Borreguero, Pablo Garcia-Roves, Ana S. H. Costa, Christian Frezza, Michael P. Murphy, Kare-Olav Stenslokken, Susana Cadenas
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Alexander Hooftman, Christian G. Peace, Dylan G. Ryan, Emily A. Day, Ming Yang, Anne F. McGettrick, Maureen Yin, Erica N. Montano, Lihong Huo, Juliana E. Toller-Kawahisa, Vincent Zecchini, Tristram A. J. Ryan, Alfonso Bolado-Carrancio, Alva M. Casey, Hiran A. Prag, Ana S. H. Costa, Gabriela de los Santos, Mariko Ishimori, Daniel J. Wallace, Swamy Venuturupalli, Efterpi Nikitopoulou, Norma Frizzell, Cecilia Johansson, Alexander Von Kriegsheim, Michael P. Murphy, Caroline Jefferies, Christian Frezza, Luke A. J. O'Neill
Summary: Metabolic rewiring through an inflammatory aspartate-argininosuccinate shunt induces fumarate-mediated protein succination and inflammatory effects in macrophages. Inhibition of fumarate hydratase (FH) increases fumarate levels, suppresses mitochondrial respiration, and enhances interferon responses. FH inhibition may play a pathogenic role in systemic lupus erythematosus. These findings highlight the importance of FH in regulating macrophage functions and cytokine responses.
Article
Multidisciplinary Sciences
Vincent Zecchini, Vincent Paupe, Irene Herranz-Montoya, Joelle Janssen, Inge M. N. Wortel, Jordan L. Morris, Ashley Ferguson, Suvagata Roy Chowdury, Marc Segarra-Mondejar, Ana S. H. Costa, Goncalo C. Pereira, Laura Tronci, Timothy Young, Efterpi Nikitopoulou, Ming Yang, Dora Bihary, Federico Caicci, Shun Nagashima, Alyson Speed, Kalliopi Bokea, Zara Baig, Shamith Samarajiwa, Maxine Tran, Thomas Mitchell, Mark Johnson, Julien Prudent, Christian Frezza
Summary: The loss of FH in the kidney leads to early changes in mitochondrial morphology and the release of mtDNA into the cytosol, which activates the cGAS-STING-TBK1 pathway and induces an inflammatory response. This phenomenon is mediated by mitochondrial-derived vesicles and depends on SNX9. These findings demonstrate that increased levels of intracellular fumarate trigger a remodelling of the mitochondrial network and the generation of mitochondrial-derived vesicles, resulting in the release of mtDNA in the cytosol and the activation of the innate immune response.
Article
Endocrinology & Metabolism
Maria Elena Steidl, Elisa A. A. Nigro, Anne Kallehauge Nielsen, Roberto Pagliarini, Laura Cassina, Matteo Lampis, Christine Podrini, Marco Chiaravalli, Valeria Mannella, Gianfranco Distefano, Ming Yang, Mariam Aslanyan, Giovanna Musco, Ronald Roepman, Christian Frezza, Alessandra Boletta
Summary: Primary cilia respond to nutrient availability by adjusting their length through glutamine-mediated anaplerosis facilitated by asparagine synthetase (ASNS). Depriving cells of nutrients causes ciliary elongation, mediated by reduced mitochondrial function and ATP availability, independently of mTORC1. Cells lacking cilia show reduced glutamine-dependent mitochondrial anaplerosis during metabolic stress.
Article
Biochemistry & Molecular Biology
Almudena Serrano-Benitez, Sophie E. Wells, Lylah Drummond-Clarke, Lilian C. Russo, John Christopher Thomas, Giovanna A. Leal, Mark Farrow, James Michael Edgerton, Shankar Balasubramanian, Ming Yang, Christian Frezza, Amit Gautam, Jan Brazina, Kamila Burdova, Nicolas C. Hoch, Stephen P. Jackson, Keith W. Caldecott
Summary: DNA single-strand breaks (SSBs) play a role in disrupting DNA replication and causing chromosome breakage. This study investigates whether SSBs induce chromosome breakage when located behind or ahead of replication forks, and finds that only SSBs ahead of replication forks trigger fork collapse and chromosome breakage. Furthermore, the study shows that CldU, a thymidine analogue, is cytotoxic to cells lacking SSB repair mechanisms and its incorporation in template DNA is particularly harmful during the following cell cycle. Additionally, BRCA-defective cells are highly sensitive to CldU, suggesting its potential clinical utility.
Article
Biochemistry & Molecular Biology
Patricia Sanchez-Perez, Ana Mata, May-Kristin Torp, Elia Lopez-Bernardo, Christina M. Heiestad, Jan Magnus Aronsen, Antonio Molina-Iracheta, Luis J. Jimenez-Borreguero, Pablo Garcia-Roves, Ana S. H. Costa, Christian Frezza, Michael P. Murphy, Kare-Olav Stenslokken, Susana Cadenas
Summary: Myocardial ischemia-reperfusion injury can lead to cardiomyocyte dysfunction, and mitochondria play a critical role in cardiomyocyte recovery. This study investigated the effects of UCP3 deficiency on functional, structural, and metabolic cardiac remodeling after IR. The results showed that UCP3 deficiency increases myocardial damage by promoting superoxide generation and mitochondrial structural changes.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Clinical Neurology
Jakob V. E. Gerstl, Sarah E. Blitz, Qing Rui Qu, Alexander G. Yearley, Philipp Lassaren, Rebecca Lindberg, Saksham Gupta, Ari D. Kappel, Juan C. Vicenty-Padilla, Edoardo Gaude, Kunakorn C. Atchaneeyasakul, Shashvat M. Desai, Dileep R. Yavagal, Luca Peruzzotti-Jametti, Nirav J. Patel, Mohammed A. Aziz-Sultan, Rose Du, Timothy R. Smith, Joshua D. Bernstock
Summary: The global macroeconomic consequences of stroke in 2019 were significant, reaching $2059.67 billion or 1.66% of the global GDP. Central European, Eastern European, and Central Asian regions reported the highest economic losses due to stroke, while Southeast Asian, East Asian, and Oceanian regions had the highest economic losses due to intracerebral hemorrhage.
Article
Cell Biology
Connor Rogerson, Marco Sciacovelli, Lucas A. Maddalena, Andromachi Pouikli, Marc Segarra-Mondejar, Lorea Valcarcel-Jimenez, Christina Schmidt, Ming Yang, Elena Ivanova, Joshua Kent, Ariane Mora, Danya Cheeseman, Jason S. Carroll, Gavin Kelsey, Christian Frezza
Summary: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a cancer syndrome caused by inactivating germ-line mutations in fumarate hydratase (FH) and subsequent accumulation of fumarate. Fumarate accumulation leads to profound epigenetic changes and the activation of an antioxidant response via nuclear translocation of the transcription factor NRF2. The identification of FOXA2 as an antioxidant regulator provides additional insights into the molecular mechanisms behind cell responses to fumarate accumulation and potentially provides further avenues for therapeutic intervention for HLRCC.
Article
Biochemistry & Molecular Biology
Srinivasa R. Rao, Andrew Protheroe, Lucia Cerundolo, David Maldonado-Perez, Lisa Browning, Alastair D. Lamb, Richard J. Bryant, Ian G. Mills, Dan J. Woodcock, Freddie C. Hamdy, Ian P. M. Tomlinson, Clare Verrill
Summary: Prostate cancer can present in different types, including acinar adenocarcinoma, neuroendocrine, and ductal carcinoma, which are associated with aggressive disease. By sequencing archival tissue, two cases were studied, revealing a common ancestry between small-cell neuroendocrine and ductal prostatic carcinoma. A patient with treatment-related neuroendocrine prostate carcinoma also showed genetic alterations associated with poor prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Maria Fala, Susana Ros, Ashley Sawle, Jyotsna U. Rao, Anastasia Tsyben, Laura Tronci, Christian Frezza, Richard Mair, Kevin M. Brindle
Summary: BCAT1 expression in glioblastoma varies widely, and its role in cell proliferation and invasion depends on the tumor subtype.
NEURO-ONCOLOGY ADVANCES
(2023)