Review
Immunology
Hengwei Wu, He Huang, Yanmin Zhao
Summary: Cellular metabolism plays a crucial role in determining cell fate and function, and metabolic reprogramming has a complex impact on cellular activities. In quiescent T cells, oxidative phosphorylation (OXPHOS) is the primary survival pathway, but upon antigen activation, T cells undergo rapid metabolic reprogramming characterized by increased glycolysis and OXPHOS. This review focuses on the metabolic reprogramming of T cells, explores the interplay between lactate and the immune system, highlights the impact of lactylation on cellular function, and elucidates the intersection of metabolic reprogramming and epigenetics.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jinxia Lin, Shicong Wang, Wenliang Lan, Ming Ji, Mei Li
Summary: This study compared the effects of the Chinese medicine formula Pien Tze Huang (PZH) and the anti-tumor drug sorafenib on hepatocellular carcinoma (HCC). It found that PZH and sorafenib both have anti-tumor effects through metabolic regulation, but differ in the regulation of some metabolic nodes.
SCIENTIFIC REPORTS
(2023)
Article
Plant Sciences
Xiaoning Yan, Jie Liu, Meixia Zhu, Lirong Liu, Yijun Chen, Yinhuan Zhang, Menghan Feng, Zhixin Jia, Hongbin Xiao
Summary: The study revealed that components of Rhodiola crenulata can induce metabolic reprogramming by regulating the Hif-1 alpha signaling pathway, activating compensatory responses. Microglia sensed low oxygen levels earlier than neurons, accompanied by elevated expression of Hif-1 alpha protein.
PHARMACEUTICAL BIOLOGY
(2021)
Article
Cell Biology
Xiukun Hou, Xianle Shi, Wei Zhang, Dapeng Li, Linfei Hu, Jihong Yang, Jingzhu Zhao, Songfeng Wei, Xi Wei, Xianhui Ruan, Xiangqian Zheng, Ming Gao
Summary: High expression levels of LDHA in papillary thyroid carcinoma are associated with aggressive clinicopathological features and poor prognosis. LDHA promotes cancer cell migration, invasion, and proliferation, making it a potential therapeutic target.
CELL DEATH & DISEASE
(2021)
Article
Cell Biology
Pravat Kumar Parida, Mauricio Marquez-Palencia, Vidhya Nair, Akash K. Kaushik, Kangsan Kim, Jessica Sudderth, Eduardo Quesada-Diaz, Ambar Cajigas, Vamsidhara Vemireddy, Paula Gonzalez-Ericsson, Melinda E. Sanders, Bret C. Mobley, Kenneth Huffman, Sunati Sahoo, Prasanna Alluri, Cheryl Lewis, Yan Peng, Robert M. Bachoo, Carlos L. Arteaga, Ariella B. Hanker, Ralph J. DeBerardinis, Srinivas Malladi
Summary: Metabolic diversity and plasticity within brain-tropic cells play a crucial role in determining the metastatic fitness of HER2+ breast cancer patients. Lactate secretion by aggressive metastatic cells or lactate supplementation inhibits innate immunosurveillance and promotes overt metastasis. Inhibiting lactate metabolism can impede brain metastasis, but some brain metastatic cells adapt and survive through specific metabolic pathways. xCT, an amino acid transporter, is significantly upregulated in brain metastatic cells compared to primary tumors, and targeting xCT can attenuate residual disease and recurrence.
Article
Cell & Tissue Engineering
Pihu Mehrotra, Izuagie Ikhapoh, Pedro Lei, Georgios Tseropoulos, Yali Zhang, Jianmin Wang, Song Liu, Marianne E. Bronner, Stelios T. Andreadis
Summary: Neural crest-like stem cells derived from adult human tissues can maintain their multipotency and enhance their differentiation potential by activating Wnt and BMP signaling and metabolic reprogramming, suggesting potential implications for regenerative medicine.
Article
Food Science & Technology
Lei Huang, Canxia He, Sicong Zheng, Chao Wu, Minghua Ren, Yujuan Shan
Summary: Sulforaphane (SFN) reduces ATP production in bladder cancer cells by inhibiting glycolysis and mitochondrial oxidative phosphorylation. SFN weakens glycolytic flux by suppressing metabolic enzymes such as hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH). Additionally, SFN downregulates the unique glucose transport aberrant-independent aerobic glycolysis in bladder cancer through the AKT1/HK2 axis and PDH expression.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Andrea Balboni, Marzia Govoni, Valentina Rossi, Marinella Roberti, Andrea Cavalli, Giuseppina Di Stefano, Marcella Manerba
Summary: The research revealed an LDH-mediated control of HR repair, independent of cell metabolic assets. LDH involvement in the DNA damage response suggests potential for new drug combinations for improved antineoplastic effects.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Review
Oncology
Thomas N. Seyfried, Gabriel Arismendi-Morillo, Giulio Zuccoli, Derek C. Lee, Tomas Duraj, Ahmed M. Elsakka, Joseph C. Maroon, Purna Mukherjee, Linh Ta, Laura Shelton, Dominic D'Agostino, Michael Kiebish, Christos Chinopoutos
Summary: Glioblastoma relies on fermentation metabolism for energy and biomass synthesis, contributing to an acidified microenvironment and drug resistance. Treatment methods for GBM can further acidify the microenvironment, but restricting glucose and glutamine while increasing non-fermentable ketone bodies may provide a non-toxic therapeutic strategy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rehab S. Abdelrahman, Noha M. Shawky
Summary: This study investigates the effects of the metabolic modulator trimetazidine (TMZ) on silica-induced pulmonary fibrosis using a rat model. The results demonstrate that TMZ attenuates silica-induced pulmonary fibrosis by suppressing excessive lactate production and regulating oxidative stress.
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
(2022)
Article
Multidisciplinary Sciences
Ekta Agarwal, Aaron R. Goldman, Hsin-Yao Tang, Andrew V. Kossenkov, Jagadish C. Ghosh, Lucia R. Languino, Valentina Vaira, David W. Speicher, Dario C. Altieri
Summary: Parkin, an E3 ubiquitin ligase altered in Parkinson's disease, is shown to suppress tumor growth by shutting off mitochondrial dynamics and inhibiting the non-oxidative phase of the pentose phosphate pathway. This tumor suppression function of Parkin requires its E3 ligase activity and can be reversed by antioxidants, independently of mitophagy. Cancer metabolic networks are identified as potential oncogenes directly targeted by endogenous tumor suppression mechanisms.
Review
Oncology
Seyedeh Sahar Mortazavi Farsani, Vivek Verma
Summary: New research reveals that not only cancer cells but also other cell types, including immune cells, exhibit the Warburg effect, converting glucose to lactate even in the presence of sufficient oxygen. Lactate plays a crucial role in metabolism and cell signaling, but high levels can inhibit immune cell function.
FRONTIERS IN ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Juan Liu, Cen Zhang, Tianliang Zhang, Chun-Yuan Chang, Jianming Wang, Ludvinna Bazile, Lanjing Zhang, Bruce G. G. Haffty, Wenwei Hu, Zhaohui Feng
Summary: The glycolytic enzyme lactate dehydrogenase A (LDHA) activates small GTPase Rac1 to promote cancer independently of its glycolytic enzyme activity. LDHA interacts with the active form of Rac1, Rac1-GTP, to inhibit Rac1-GTP interaction with its negative regulator, GTPase-activating proteins, leading to Rac1 activation. LDHA overexpression in clinical breast cancer specimens is associated with higher Rac1 activity. Inhibition of Rac1 suppresses the oncogenic effect of LDHA. Combination inhibition of LDHA enzyme activity and Rac1 activity displays a synergistic inhibitory effect on breast cancers with LDHA overexpression.
Article
Cell Biology
Beatriz Fernandez-Gil, Andrea Otamendi-Lopez, Alexandra Bechtle, Carla A. Vazquez-Ramos, Neda Qosja, Paola Suarez-Meade, Rachel Sarabia-Estrada, Mark E. Jentoft, Hugo Guerrero-Cazares, Germaine Escames, Paula Schiapparelli, Alfredo Quinones-Hinojosa
Summary: This study reveals that melatonin inhibits the proliferation and survival of GBM tumor initiating cells by modulating intracellular pH and inducing cellular death. These findings provide new insights into the oncostatic effect of melatonin on GBM and may contribute to the development of new therapeutic strategies.
Article
Microbiology
Lujie Zhang, Xing Liu, Jian Mao, Yangyang Sun, Yanni Gao, Juan Bai, Ping Jiang
Summary: Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen in the global pig industry, causing reproductive failure and respiratory problems. This study found that high glucose promotes PRRSV replication by inhibiting interferon signaling, while inhibition of the glycolysis pathway suppresses viral replication and enhances immune response. PRRSV also promotes glycolysis to produce lactate, which targets MAVS to inhibit immune signaling and promote viral replication. These findings provide insights into the pathogenesis of PRRSV and offer potential therapeutic targets for antiviral development.
VETERINARY MICROBIOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Nicolas Huber, Edgar Alberto Alcala-Orozco, Thomas Rexer, Udo Reichl, Steffen Klamt
Summary: Cell-free production systems are commonly used for synthesizing industrial chemicals and biopharmaceuticals. This study presents a model-based optimization framework for cell-free enzyme cascades, taking into account parameter uncertainties. The approach was exemplified using the synthesis of GDP-fucose, resulting in significant improvements in the process.
METABOLIC ENGINEERING
(2024)