Article
Biochemistry & Molecular Biology
Giuseppe Cannino, Andrea Urbani, Marco Gaspari, Mariaconcetta Varano, Alessandro Negro, Antonio Filippi, Francesco Ciscato, Ionica Masgras, Christoph Gerle, Elena Tibaldi, Anna Maria Brunati, Giorgio Colombo, Giovanna Lippe, Paolo Bernardi, Andrea Rasola
Summary: This study reveals that the mitochondrial chaperone TRAP1 interacts with F-ATP synthase, increasing its catalytic activity and counteracting the inhibitory effect of CyPD. Additionally, TRAP1 directly inhibits the channel activity of F-ATP synthase and reverses PTP induction by CyPD, thus preventing mitochondrial depolarization and cell death. These findings highlight the importance of TRAP1 in cell bioenergetics and survival.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Chemistry, Medicinal
Soosung Kang, Byoung Heon Kang
Summary: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that modulates cellular metabolism and signaling pathways. It can alter the conformation, activity, and stability of various substrate proteins. TRAP1 has been proposed as a promising target for anticancer drug development, but dysregulation of its stress-adaptive machinery may contribute to the progression and maintenance of human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Xueran Chen, Wanxiang Niu, Xiaoqing Fan, Haoran Yang, Chenggang Zhao, Junqi Fan, Xuebiao Yao, Zhiyou Fang
Summary: In this study, it was found that Oct4A can impact the tumorigenic activity of glioblastoma and its stability is maintained through palmitoylation. Oct4A palmitoylation helps to integrate Sox4 and Oct4A in the SOX2 enhancement subregion, thereby maintaining the stem performance of glioma stem cells. The study also designed Oct4A palmitoylation competitive inhibitors that can inhibit the self-renewal ability and tumorigenicity of glioma stem cells.
Article
Biochemistry & Molecular Biology
Benjamin E. Clarke, Bernadett Kalmar, Linda Greensmith
Summary: Overexpression of TRAP1 can protect motor neurons from mitochondrial dysfunction and death induced by oxidative stress, suggesting it as a potential therapeutic target for neurodegenerative diseases like ALS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Aida Rodriguez-Nuevo, Ariadna Torres-Sanchez, Juan M. Duran, Cristian De Guirior, Maria Angeles Martinez-Zamora, Elvan Boke
Summary: Oocytes evade the negative effects of reactive oxygen species (ROS) by eliminating complex I in the mitochondrial electron transport chain. Early oocytes have low levels of complex I and an active mitochondrial unfolded protein response. This suppression of complex I represents a strategy for maintaining biological activity while achieving longevity.
Article
Biochemistry & Molecular Biology
Olivier Lurette, Hala Guedouari, Jordan L. Morris, Rebeca Martin-Jimenez, Julie-Pier Robichaud, Genevieve Hamel-Cote, Mehtab Khan, Nicholas Dauphinee, Nicolas Pichaud, Julien Prudent, Etienne Hebert-Chatelain
Summary: The architecture of mitochondria is regulated by the tyrosine kinase Src, which affects mitochondrial morphology independently of mitochondrial size, cellular respiration, or ATP levels. This study highlights a novel function for Src in the control of mitochondrial dynamics.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ines Ramos Rego, Daniela Silverio, Maria Isabel Eufrasio, Sandra Sofia Pinhancos, Bruna Lopes da Costa, Jose Teixeira, Hugo Fernandes, Yang Kong, Yao Li, Stephen H. Tsang, Paulo J. Oliveira, Rosa Fernandes, Peter M. J. Quinn, Paulo Fernando Santos, Antonio Francisco Ambrosio, Celso Henrique Alves
Summary: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness in the elderly. The damage to retinal pigment epithelium (RPE) caused by oxidative stress is a key factor in the development of AMD, and this damage is caused by the accumulation of reactive oxygen species (ROS) primarily produced by mitochondria. The protein TRAP1, found in mitochondria, helps maintain mitochondrial integrity and reduces ROS production. This study found that TRAP1 is present in human RPE cells and its levels decrease when exposed to hydrogen peroxide. Silencing TRAP1 leads to increased ROS production and decreased mitochondrial respiratory capacity in RPE cells.
Article
Medicine, Research & Experimental
Demiana H. Sami, Ayman S. Soliman, Akef A. Khowailed, Emad H. M. Hassanein, Emadeldin M. Kamel, Ayman M. Mahmoud
Summary: In this study, the protective effect of the antioxidant 7-hydroxycoumarin (7-HC) against cisplatin-induced acute kidney injury was investigated. Results showed that 7-HC prevented kidney dysfunction and tissue injury, suppressed oxidative stress and inflammation, and modulated several signaling pathways. Molecular docking revealed the potential binding of 7-HC to specific proteins involved in these pathways.
Article
Biochemistry & Molecular Biology
Siqi Liu, Shanshan Liu, Baiyu He, Lanlan Li, Lin Li, Jiawen Wang, Tao Cai, She Chen, Hui Jiang
Summary: The research reveals that yeast mutants deficient in certain oxidative phosphorylation complexes and mtDNA exhibit progressive reduction of mitochondrial membrane potential. These mutants activate adaptive responses, including remodeling of mitochondrial proteome and reshaping of cellular metabolism.
Article
Medicine, Research & Experimental
Zhen Liu, Jiaxin Lei, Tong Wu, Weijie Hu, Ming Zheng, Ying Wang, Jingdong Song, Hang Ruan, Lin Xu, Tao Ren, Wei Xu, Zhenke Wen
Summary: Cancer stem-like cells (CSCs) play a critical role in cancer metastasis and chemoresistance, posing a major challenge in clinical practice. In this study, it was found that human lung CSCs exhibit metabolic reprogramming characterized by enhanced lipogenesis and mitochondrial fusion regulated by OPA1. Transcription factor SPDEF induces OPA1 expression, promoting mitochondrial fusion and the stemness of CSCs. Blocking lipogenesis and mitochondrial fusion can effectively inhibit the growth and expansion of CSCs in lung cancer patients.
Article
Cell Biology
Cristina Cueto-Urena, Enric Mocholi, Josep Escriva-Fernandez, Susana Gonzalez-Granero, Sabina Sanchez-Hernandez, Amalia Solana-Orts, Begona Ballester-Lurbe, Karim Benabdellah, Rosa M. Guasch, Jose Manuel Garcia-Verdugo, Francisco Martin, Paul J. Coffer, Ignacio Perez-Roger, Enric Poch
Summary: This study reveals that loss of Rnd3 expression affects mitochondrial oxidative metabolism and renders cells dependent on glycolysis for energy, suggesting a possible connection to neurodegenerative diseases.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Immunology
Madison Schank, Juan Zhao, Ling Wang, Lam Ngoc Thao Nguyen, Dechao Cao, Xindi Dang, Sushant Khanal, Jinyu Zhang, Yi Zhang, Xiao Y. Wu, Shunbin Ning, Mohamed El Gazzar, Jonathan P. Moorman, Zhi Q. Yao
Summary: Chronic HCV infection can lead to compromised mitochondrial functions in CD4 T cells, likely through the dysregulation of several mitochondrial regulatory proteins.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Neurosciences
Fahim Atif, Seema Yousuf, Claudia Espinosa-Garcia, Donald G. Stein
Summary: Research shows that high doses of progesterone have an inhibitory effect on mitochondrial respiration and glycolysis in glioblastoma multiforme cells, potentially leading to decreased tumor size and growth rate.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jordan M. Johnson, Alek D. Peterlin, Enrique Balderas, Elahu G. Sustarsic, J. Alan Maschek, Marisa J. Lang, Alejandro Jara-Ramos, Vanja Panic, Jeffrey T. Morgan, Claudio J. Villanueva, Alejandro Sanchez, Jared Rutter, Irfan J. Lodhi, James E. Cox, Kelsey H. Fisher-Wellman, Dipayan Chaudhuri, Zachary Gerhart-Hines, Katsuhiko Funai
Summary: Phosphatidylethanolamine (PE) modulates the proton conductance of UCP1, regulating thermogenesis in brown adipose tissue (BAT).
Article
Biochemistry & Molecular Biology
Ivan Milenkovic, Helaine Graziele Santos Vieira, Morghan C. Lucas, Jorge Ruiz-Orera, Giannino Patone, Scott Kesteven, Jianxin Wu, Michael Feneley, Guadalupe Espadas, Eduard Sabido, Norbert Huebner, Sebastiaan van Heesch, Mirko Voelkers, Eva Maria Novoa
Summary: The study investigates the existence of ribosome heterogeneity and its potential impact on specialized ribosomes. Through analyzing a knockout mouse strain, the researchers find that the depletion of RPL3L leads to an up-regulation of RPL3, resulting in the formation of RPL3-containing ribosomes in cardiomyocytes. Additionally, they discover that RPL3L depletion increases interactions between ribosomes and mitochondria, leading to elevated ATP levels.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Sangpil Kim, Nam Gu Yoon, Batakrishna Jana, Byoung Heon Kang, Ja-Hyoung Ryu
Summary: Novel mitochondria targeting agents with high water solubility were designed by introducing quaternary ammonium, which effectively inhibit mitochondrial respiratory chain and induce apoptosis in cancer cells. These agents have the potential to be developed as anticancer drugs.
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Sujae Yang, Nam Gu Yoon, Min-A Park, Jisu Yun, Jin Young Im, Byoung Heon Kang, Soosung Kang
Summary: TRAP1, overexpressed in many cancer cells, supports tumorigenesis by rewiring vital metabolic and cell death pathways. Compound 6a, a TRAP1-selective inhibitor, shows potent anticancer activity in multiple cancer cell lines and suppresses tumor growth in a nude mouse model.
BIOORGANIC CHEMISTRY
(2022)
Article
Clinical Neurology
Ye Yoon Suh, Kwanghoon Lee, Yu-Mi Shim, Ji Hoon Phi, Chul-Kee Park, Seung-Ki Kim, Seung Hong Choi, Hongseok Yun, Sung-Hye Park
Summary: The MYB/MYBL1::QKI fusion activates the oncogene MYB and deletes the tumor suppressor gene QKI. Previously, this fusion was only reported in angiocentric glioma (AG) and diffuse low-grade glioma. This study compares two tumors with the MYB/MYBL1::QKI fusion: a diffuse pediatric-type high-grade glioma (DPedHGG) in an 11-year-old boy and an AG in a 46-year-old woman. Characterization using immunohistochemistry, next-generation sequencing, and methylation profiling reveals their molecular characteristics and supports the presence of MYB/MYBL1 alterations in higher-grade gliomas.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Oncology
Aram Ko, Mohammad Hasanain, Young Taek Oh, Fulvio D'Angelo, Danika Sommer, Brulinda Frangaj, Suzanne Tran, Franck Bielle, Bianca Pollo, Rosina Paterra, Karima Mokhtari, Rajesh Kumar Soni, Matthieu Peyre, Marica Eoli, Laura Papi, Michel Kalamarides, Marc Sanson, Antonio Iavarone, Anna Lasorella
Summary: LZTR1 is a substrate-specific adaptor of a CUL3-dependent ubiquitin ligase frequently mutated in cancer. The study identified EGFR and AXL as LZTR1 substrates targeted for degradation, and found that LZTR1 mutations result in the accumulation and deregulated signaling of EGFR and AXL. The study also revealed vulnerabilities of LZTR1-mutant tumors to inhibition of EGFR and AXL, providing precision targeting for patients with LZTR1-mutant cancer.
Article
Genetics & Heredity
Xiong Jin, Jianlei Kang, Qing Lu, Shuang-Lei Guo, Meichen Liu, Yue Zhang, Can Cui, Hong-Lin Liu, Xin Xu, Jinlong Yin
Summary: This study identified Fc gamma RIIb as a potential driver for recurrent GBM based on gene expression analysis. Further investigations revealed a highly negative correlation between FCGR2B expression and poor prognosis in patients with recurrent GBM. The study also found that Fc gamma RIIb was strongly associated with immune-related signaling pathways and expressed in tumor-associated macrophages and dendritic cells. These findings provide novel insights into the role of Fc gamma RIIb in recurrent GBM and suggest it as a promising immune therapeutic target.
FRONTIERS IN GENETICS
(2023)
Article
Multidisciplinary Sciences
Weiwei Lin, Rui Niu, Seong-Min Park, Yan Zou, Sung Soo Kim, Xue Xia, Songge Xing, Qingshan Yang, Xinhong Sun, Zheng Yuan, Shuchang Zhou, Dongya Zhang, Hyung Joon Kwon, Saewhan Park, Chan Il Kim, Harim Koo, Yang Liu, Haigang Wu, Meng Zheng, Heon Yoo, Bingyang Shi, Jong Bae Park, Jinlong Yin
Summary: The IGFBP5-ROR1/HER2-CREB signaling axis is a potential therapeutic target for glioblastoma (GBM) to inhibit the invasion capacity and gene expression of GBM stem-like cells (GSCs) and suppress tumor growth.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Yejin Kim, Chulhwan Kwak, Jong Bae Park, Do-Hyun Nam, Hyun-Woo Rhee, Sung Soo Kim
Summary: Adapted oxidative phosphorylation and tricarboxylic acid cycle activations play crucial roles in tumor microenvironments for abnormal energy consumption in cancer development and drug resistance. A longitudinal GBM mouse model with acquired resistance to bevacizumab was established to investigate the molecular mechanism related to mitochondrial metabolic dynamics and drug resistance in GBM. Proteomic analysis revealed enrichment of OXPHOS, TCA, and calcium signaling gene sets in the bevacizumab pre-resistance phase. Additionally, targeting the MCU protein, a pore-forming subunit of the mitochondrial calcium uniporter, showed promising therapeutic potential in combination with bevacizumab in recurrent GBM.
ADVANCED THERAPEUTICS
(2023)
Editorial Material
Clinical Neurology
M. E. Buckland, C. Sarkar, V. Santosh, M. Al-Hussaini, S. H. Park, T. Tihan, H. K. Ng, T. Komori
Article
Clinical Neurology
Tae-Hwan Park, Kyung Hyun Kim, Seung-Ki Kim, Kyu-Chang Wang, Sung-Hye Park, Ji Yeoun Lee
Summary: Fibrous hamartoma of infancy (FHI) is a rare benign soft tissue lesion that usually occurs in infants and young children within the first 2 years of life. FHI in the central nervous system (CNS) is extremely rare, with only two cases of spinal cord FHI reported so far. We present a unique case of FHI in a 1-month-old girl with a skin dimple in the coccygeal area, where both a skin lesion and an intramedullary mass were diagnosed as FHI. Despite being diagnosed with a neurogenic bladder, the patient maintained normal neurological function and showed good mobility during the 5.5-year follow-up period.
CHILDS NERVOUS SYSTEM
(2023)
Review
Clinical Neurology
Hyunhee Kim, Kwanghoon Lee, Ji Hoon Phi, Sun Ha Paek, Hongseok Yun, Seung Hong Choi, Sung-Hye Park
Summary: This study presents the clinicopathological and molecular genetic characteristics of a neuroepithelial tumor (NET) with EWSR1::PATZ1 fusion, which has recently been discovered in rare central nervous system tumors and soft tissue sarcomas. Two cases of this fusion were identified, with the pediatric case showing a high-grade tumor and longer survival compared to conventional glioblastoma. The TERT promoter mutation may serve as an indicator of high-grade behavior in PATZ1 fusion NET.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2023)
Article
Medicine, Research & Experimental
Hyunhee Kim, Kwanghoon Lee, Yu -Mi Shim, Eric Eunshik Kim, Seung-Ki Kim, Ji Hoon Phi, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park
Summary: Central neurocytoma is a low-grade neuronal tumor that mainly occurs in the lateral ventricle, and the genetic abnormalities that cause this tumor are poorly understood. Through the study of immunomarkers in fetal and adult brains, as well as supratentorial periventricular tumors, the biomarkers, cell of origin, and tumorigenesis of central neurocytoma were characterized. Immunohistochemical analysis showed that central neurocytomas were positive for certain markers, including FGFR3, SSTR2, TTF-1, GLUT-1, and L1CAM.
LABORATORY INVESTIGATION
(2023)
Article
Biochemistry & Molecular Biology
Hyeongsun Jeong, Hyo Eun Moon, Seongmin Yun, Seung Woo Cho, Hye Ran Park, Sung-Hye Park, Kyungjae Myung, Taejoon Kwon, Sun Ha Paek
Summary: In this study, 13 PDX models derived from 11 brain tumor patients were established. It was found that PDX samples were enriched with brain tumor-related genes and had distinct mutation profiles compared to the original tumors, indicating mutational alterations occurring in the xenograft environment.
Article
Pharmacology & Pharmacy
Yejin Kim, Tae Hoon Kim, Srun Sreynet, Yong Seok Oh, Do-Hyun Nam, Jong Bae Park, Sung Soo Kim
Summary: This study conducted a translatomic analysis on pseudopalisading cells in brain tumors and found that these cells are associated with neurodegenerative diseases. The results of this study provide important insights into the molecular mechanism of resistance induced by bevacizumab treatment.
ADVANCED THERAPEUTICS
(2023)
Review
Medicine, General & Internal
Jin Woo Park, Kwanghoon Lee, Eric Eunshik Kim, Seong-Ik Kim, Sung-Hye Park
Summary: The methylation classifier is a tool used to accurately classify brain tumors based on their methylation profiles. It helps healthcare professionals predict tumor prognosis and establish personalized treatment plans. However, it has limitations in classifying all types of brain tumors and faces challenges in obtaining reference data and charging patients for its services.
JOURNAL OF KOREAN MEDICAL SCIENCE
(2023)