Article
Oncology
Yun-Rong Zhu, Xiang-Yang Zhang, Qiu-Ping Wu, Cheng-Jian Yu, Yuan-Yuan Liu, Yun-Qing Zhang
Summary: Activation of AMPK by PF-06409577 inhibits the growth of osteosarcoma cells, inducing cell apoptosis and cell cycle arrest.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cell Biology
Sumati Hasani, Lyndsay E. A. Young, Warren Van Nort, Moumita Banerjee, Dylan R. Rivas, Jinhwan Kim, Xiaopeng Xiong, Ramon C. Sun, Matthew S. Gentry, Hiromi Sesaki, Tianyan Gao
Summary: Loss of Drp1 activates compensative metabolic pathways, glucose uptake and glycogenesis, to promote cell survival in colon cancer.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Sumei Li, Jingxiang Wang, Yurong Lu, Yuqing Zhao, Richard A. Prinz, Xiulong Xu
Summary: Inhibition of the Shh pathway induces autophagy in thyroid tumor cells and can affect GANT61-induced apoptosis; mechanistic investigation reveals the significant role of TAK1 in this process.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Juan Li, Hanxiang Zhan, Yidan Ren, Maoxiao Feng, Qin Wang, Qinlian Jiao, Yuli Wang, Xiaoyan Liu, Shujun Zhang, Lutao Du, Yunshan Wang, Chuanxin Wang
Summary: This study found that SIRT4 activates the phosphorylation of p53 protein and promotes autophagy in PDAC by suppressing glutamine metabolism, thereby inhibiting tumor growth and progression.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Xin Cai, Charles P. Ng, Olivia Jones, Tak Shun Fung, Keun Woo Ryu, Dayi Li, Craig B. Thompson
Summary: Lactate can enter the mitochondrial matrix and stimulate electron transport chain activity, increasing ATP synthesis and suppressing glycolysis. Unmetabolized D-lactate can reversibly inhibit oxidative phosphorylation and suppress glucose fermentation, promoting cell growth and function.
Article
Hematology
Ingrid Spaan, Laura M. Timmerman, Thomas Kimman, Anne Slomp, Marta Cuenca, Niels van Nieuwenhuijzen, Laura M. Moesbergen, Monique C. Minnema, Reinier A. Raymakers, Victor Peperzak
Summary: Novel combination therapies have significantly improved the lifespan of patients with multiple myeloma, with dexamethasone and the MCL-1 inhibitor S63845 showing the most potent combination for inducing apoptosis. Kinome analysis revealed reduced Akt activity in dexamethasone-treated cells, suggesting a potential mechanism for the combination's efficacy in treating MM.
Editorial Material
Oncology
Gourish Mondal, Jayanta Debnath
Summary: Inhibiting autophagy in pancreatic ductal adenocarcinoma cells can activate the NRF2-mediated macropinocytosis pathway, providing an alternate way for tumors to obtain nutrients from the extracellular environment. Therefore, the combined inhibition of autophagy and macropinocytosis may enhance cancer treatment outcomes.
Article
Medicine, Research & Experimental
Mona Peyman, Emma Barroso, Andreea L. Turcu, Francesc Estrany Jr, Daire Smith, Javier Jurado-Aguilar, Patricia Rada, Christophe Morisseau, Bruce D. Hammock, Angela M. Valverde, Xavier Palomer, Carles Galdeano, Santiago Vazquez, Manuel Vazquez-Carrera
Summary: This study demonstrates that targeting sEH with degraders can degrade the protein, regulate AMPK activation, and reduce ER stress and inflammation in mice.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Cell Biology
Zehan Hu, Devanarayanan Siva Sankar, Bich Vu, Alexandre Leytens, Christine Vionnet, Wenxian Wu, Michael Stumpe, Esther Martinez-Martinez, Bjoern Stork, Joern Dengjel
Summary: ULK1 kinase complex is a key regulator of autophagy, phosphorylating autophagy-relevant proteins for autophagosome maturation and turnover. It also interacts closely with various phosphatase complexes, such as PP2A, to coordinate protein degradation through autophagy.
Article
Cell Biology
Cheng-Jung Ho, Huey-Jiun Ko, Tzu-Shao Liao, Xiang-Ren Zheng, Po-Hsu Chou, Li-Ting Wang, Ru-Wei Lin, Chung-Hwan Chen, Chihuei Wang
Summary: The study found that apoptosis induced by doxorubicin and paclitaxel in osteosarcoma cells is p53-independent, and ABT-263 can enhance the apoptotic effects of these chemotherapeutic drugs. Differential expression of Bim protein in different cells may lead to different apoptotic responses.
CELL DEATH DISCOVERY
(2021)
Article
Cell Biology
Li Ma, Weiyun Li, Yanbo Zhang, Linlin Qi, Qi Zhao, Na Li, Yao Lu, Luqing Zhang, Fei Zhou, Yichun Wu, Yongning He, Hongxiu Yu, Yulong He, Bin Wei, Hongyan Wang
Summary: Macrophages undergo glycolytic reprogramming, autophagy, inflammasome activation, and pyroptosis to eliminate invading bacteria. The FLT4-AMPK module plays a crucial role in coordinating these processes, with potential therapeutic applications.
Article
Biochemistry & Molecular Biology
Yu Zhou, Xi Liu, Caihua Huang, Donghai Lin
Summary: Lactate, a compound fuel in metabolism, remains unclear whether it plays an important role in muscle cell metabolism. This study assessed the effects of lactate on myoblasts and clarified the underlying metabolic mechanisms. The results showed that lactate treatment promoted the proliferation and differentiation of myoblasts, and regulated metabolisms by promoting lactate intake and utilization, activating the TCA cycle, and increasing energy production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Elnaz Aledavood, Aria Gheeraert, Alessia Forte, Laurent Vuillon, Ivan Rivalta, F. Javier Luque, Carolina Estarellas
Summary: AMPK is a key energy sensor that regulates cell metabolism in response to energy supply and demand. Different isoforms of AMPK formed heterotrimeric complexes exhibit notable differences in sensitivity to direct activators, with PF-739 playing a role in activating AMPK through specific mechanisms. Understanding these molecular factors can help in designing selective activators for improving tissue specificity in therapeutic treatment.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Zhibin Liang, David Soriano-Castell, Devin Kepchia, Brendan M. Duggan, Antonio Currais, David Schubert, Pamela Maher
Summary: The study demonstrates that cannabinol (CBN) can protect nerve cells from oxytosis/ferroptosis by targeting mitochondria and preserving key mitochondrial functions. These protective effects are mediated by promoting endogenous antioxidant defenses and activating AMP-activated protein kinase (AMPK) signaling. This research highlights the potential of mitochondrially-targeted compounds like CBN as novel inhibitors for mitochondrial dysfunction and neurodegenerative diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Young Eun Kim, Seon-Been Bak, Min-Jin Kim, Su-Jin Bae, Won-Yung Lee, Young Woo Kim
Summary: This study demonstrates the protective effects of forsythiaside A (FA) against oxidative stress, attenuating cell damage caused by reactive oxygen species (ROS) through the activation of AMP-activated protein kinase (AMPK) and the modulation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Shlomit Ezer, Muhannad Daana, Julien H. Park, Shira Yanovsky-Dagan, Ulrika Nordstrom, Adily Basal, Simon Edvardson, Ann Saada, Markus Otto, Vardiella Meiner, Stefan L. Marklund, Peter Munch Andersen, Tamar Harel
Summary: Pathogenic variants in the SOD1 gene are associated with a severe motor-neurological syndrome in infants, characterized by global developmental delay and movement impairments. This study identified a homozygous loss-of-function variant in the SOD1 gene in an infant with severe neurological symptoms. Further analysis showed that this variant leads to instability and degeneration of the SOD1 protein. The study highlights the importance of specific valine residues in the SOD1 protein and suggests implications for future therapeutic research.
Article
Oncology
Tammi Arbel Rubinstein, Inbal Reuveni, Arkadi Hesin, Anat Klein-Goldberg, Hannes Olauson, Tobias E. Larsson, Carmela R. Abraham, Ella Zeldich, Assumpcio Bosch, Miguel Chillon, Kenneth Samuel Hollander, Ayelet Shabtay-Orbach, Gilad W. Vainer, Ido Wolf, Tami Rubinek
Summary: The study demonstrated that klotho acts as a tumor suppressor in pancreatic ductal adenocarcinoma, with DNA methylation being correlated with patient survival. The findings suggest that sKL could serve as a therapeutic agent for pancreatic cancer.
Article
Cell Biology
Kumudesh Mishra, Maria Peter, Anna Maria Nardiello, Guy Keller, Victoria Llado, Paula Fernandez-Garcia, Ulf D. Kahlert, Dinorah Barasch, Ann Saada, Zsolt Toeroek, Gabor Balogh, Pablo V. Escriba, Stefano Piotto, Or Kakhlon
Summary: The synthetic fatty acid 2-hydroxyoleic acid (2OHOA) has been investigated for its potential as a cancer therapy. It has been found to regulate membrane lipid composition and structure, and can uncouple oxidative phosphorylation. This study explores the effects of 2OHOA on mitochondria and shows that it hydroxylates mitochondrial lipids, leading to decreased co-enzyme Q diffusion and inhibition of respiratory complex activity.
Article
Health Care Sciences & Services
Denis Horgan, Giuseppe Curigliano, Olaf Riess, Paul Hofman, Reinhard Buettner, Pierfranco Conte, Tanja Cufer, William M. Gallagher, Nadia Georges, Keith Kerr, Frederique Penault-Llorca, Ken Mastris, Carla Pinto, Jan Van Meerbeeck, Elisabetta Munzone, Marlene Thomas, Sonia Ujupan, Gilad W. Vainer, Janna-Lisa Velthaus, Fabrice Andre
Summary: Next-generation sequencing (NGS) has the potential to revolutionize cancer treatment with its personalized approach. However, the implementation of NGS in Europe varies, highlighting the need for collaboration among stakeholders. To address this issue, the European Alliance for Personalised Medicine (EAPM) established expert panels consisting of key stakeholders from 10 European countries. The panels identified challenges related to NGS demand and supply, and made recommendations for multi-stakeholder collaboration to improve patient care.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Genetics & Heredity
Shiri Liber, Orna Staretz-Chacham, Mor Kishon, Ben Pode-Shakked, Odelia Chorin, Katya Kneller, Yair Anikster, Geto Mangisto, Ann Saada, Annick Raas-Rothschild
Summary: Sanfilippo Syndrome is a lysosomal storage disorder caused by enzyme deficiency leading to tissue accumulation of heparan sulfate. It is characterized by progressive neurodegeneration and systemic manifestations. Delayed diagnosis is common, and early clinical features include speech delay, coarse facial features, and global developmental delay.
MOLECULAR SYNDROMOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Liza Douiev, Chaya Miller, Guy Keller, Hadar Benyamini, Bassam Abu-Libdeh, Ann Saada
Summary: In this study, we demonstrated that COX4-1 deficiency leads to accumulative DNA damage and premature cellular senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Genya Aharon-Hananel, Leonor Romero-Afrima, Ann Saada, Carmit Mantzur, Itamar Raz, Sarah Weksler-Zangen
Summary: The pancreatic beta-cells in Cohen diabetic-sensitive (CDs) rats exhibit decreased COX activity which correlates with reduced GSIS and increased blood glucose levels, leading to hyperglycemia when COX activity drops below 46%, but can be restored by a reversion diet. Interestingly, there is a significant correlation between COX activity in peripheral-blood mononuclear cells (PBMCs) and islets, showing potential as a noninvasive biomarker for beta-cell dysfunction monitoring in diabetes.
Article
Biochemistry & Molecular Biology
Madleen Zighan, David Arkadir, Liza Douiev, Guy Keller, Chaya Miller, Ann Saada
Summary: Omaveloxolone, a second-generation triterpenoid Nrf2 inducer, has antioxidant and anti-inflammatory properties. It has the potential to improve mitochondrial bioenergetics and could be beneficial for disorders involving mitochondrial dysfunction. In this study, Omaveloxolone was found to have effects on primary fibroblasts derived from patients with mitochondrial complex I deficiency, mitochondrial cytochrome oxidase deficiency, and recessive Parkinson's disease. However, further investigation is needed to explore its precise effects on mitochondrial function in these diseases.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemical Research Methods
Hanan Schoffman, Yishai Levin, Ayelet Itzhaki-Alfia, Lea Tselekovits, Lior Gonen, Gilad Wolf Vainer, Goni Hout-Siloni, Iris Barshack, Zvi R. Cohen, Nevo Margalit, Tal Shahar
Summary: This study compared the effects of formaldehyde-fixed paraffin-embedded (FFPE) tissue blocks and fresh frozen tissue (FFT) on the quantifiable proteome. The results showed that both methods yield a similar number of proteins, but there are significant differences in the proteome composition, with FFPE specimens enriched with smaller proteins.
Article
Endocrinology & Metabolism
Suha Daas, Nasser Abu Salah, Yair Anikster, Ortal Barel, Nadirah S. Damseh, Elena Dumin, Aviva Fattal-Valevski, Tzipora C. Falik-Zaccai, Clair Habib, Sagi Josefsberg, Stanley H. Korman, Katya Kneller, Yuval Landau, Tally Lerman-Sagie, Hanna Mandel, Yehoshua Manor, Tameemi Moady Abdalla, Rachel Rock, Nira Rostami, Ann Saada, Talya Saraf-Levy, Nava Shaul Lotan, Ronen Spiegel, Orna Staretz-Chacham, Galit Tal, Igor Ulanovsky, Taly Vaisid, Yael Wilnai, Shlomo Almashanu
Summary: Galactosemia is an inborn disorder of carbohydrate metabolism. Israeli newborn screening algorithm for galactosemia includes measurement of galactose-1-phosphate as the first-tier screening test and GALT enzyme activity as the second-tier test.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Reut Hazan (Ben-Menachem), Dvora Lintzer, Tamar Ziv, Koyeli Das, Irit Rosenhek-Goldian, Ziv Porat, Hila Ben Ami Pilo, Sharon Karniely, Ann Saada, Neta Regev-Rudzki, Ophry Pines
Summary: Vesicular transport is a means of communication between cells, and this study focuses on organelle-to-organelle communication, specifically between mitochondria. The researchers discovered that functional mitochondria in yeast can release vesicles, which are about 100 nm in size and carry selective protein cargo, including ATP synthase subunits. These vesicles also contain a functional ATP synthase complex and have the ability to fuse with naive mitochondria, potentially delivering ATP and participating in organelle-to-organelle communication.
Article
Multidisciplinary Sciences
Gilad Vainer, Lingkang Huang, Kenneth Emancipator, Shanthy Nuti
Summary: We analyzed the concordance of a laboratory-developed test (LDT) based on the 22C3 antibody with the regulatory-approved PD-L1 IHC 22C3 pharmDx in multiple tumor types. The LDT showed high agreement with the pharmDx in terms of negative percentage agreement (NPA), positive percentage agreement (PPA), and overall percentage agreement (OPA) across all tumor types. The findings suggest the comparability of the LDT with the regulatory-approved pharmDx.
Article
Oncology
Omer Goldman, Lital N. Adler, Emma Hajaj, Tommaso Croese, Naama Darzi, Sivan Galai, Hila Tishler, Yarden Ariav, Dor Lavie, Liat Fellus-Alyagor, Roni Oren, Yuri Kuznetsov, Eyal David, Rami Jaschek, Chani Stossel, Oded Singer, Sergey Malitsky, Renana Barak, Rony Seger, Neta Erez, Ido Amit, Amos Tanay, Ann Saada, Talia Golan, Tamar Rubinek, Joo Sang Lee, Shay Ben-Shachar, Ido Wolf, Ayelet Erez
Summary: Multiple studies have found metabolic changes within the tumor and its micro-environment during carcinogenesis, but the mechanisms by which tumors affect the host metabolism are unclear. This study discovered that systemic inflammation induced by cancer results in the infiltration of myeloid cells into the liver, leading to the depletion of a master metabolic regulator, HNF4α, and subsequently causing systemic metabolic changes that promote breast and pancreatic cancer proliferation.
Article
Cell Biology
Sahar Sweetat, Keren Nitzan, Nir Suissa, Yael Haimovich, Michal Lichtenstein, Samar Zabit, Sandrine Benhamron, Karameh Akarieh, Kumudesh Mishra, Dinorah Barasch, Ann Saada, Tamar Ziv, Or Kakhlon, Haya Lorberboum-Galski, Hanna Rosenmann
Summary: We investigated the efficacy of mitochondrial transfer in 5XFAD transgenic mice and found that it improved cognitive impairment, reduced amyloid burden, and alleviated mitochondrial dysfunction. The exogenously injected mitochondria were detected in the liver, but not in the brain. We observed changes in the brain proteome and liver metabolome, suggesting that the beneficial effects of mitochondrial transfer may be mediated by metabolic signaling from the liver to the brain via the serum. These findings highlight the potential of mitochondrial transfer as a novel therapy for Alzheimer's disease.
Meeting Abstract
Biochemistry & Molecular Biology
Emuna Paz, Hagar Mor-Shaked, Adily Basal, Simona Ben-Haim, Hanna Grobe, Sami Heymann, Zvi Israel, Vardiella Meiner, Montaser Namnah, Anat Nitzan, Ann Saada, Tomer Tzur, Ronen Zaidel-Bar, Tamar Harel, David Arkadir
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
