Review
Biochemistry & Molecular Biology
Verica Paunovic, Milica Kosic, Maja Misirkic-Marjanovic, Vladimir Trajkovic, Ljubica Harhaji-Trajkovic
Summary: Tumor cells increase energy-producing pathways and lysosomal activity to sustain their proliferative and metastatic capacity, making large fragile lysosomes and enhanced energy metabolism potential targets for anticancer therapy. Simultaneously inducing energy stress and lysosomal stress has been shown to be an effective anti-cancer strategy.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Environmental Sciences
Zhaoqi He, Peng Shen, Lianjun Feng, Haoyang Hao, Yuhong He, Guyue Fan, Zhuoyu Liu, Kun Zhu, Yiqi Wang, Naisheng Zhang, Xiaoyu Hu, Yunhe Fu, Jiacheng Wu
Summary: Cadmium-induced liver toxicity is associated with ferroptosis, which is involved in oxidative stress, autophagy, and endoplasmic reticulum stress.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Environmental Sciences
Ting Zhang, Jie Lu, Ying Yao, Yanting Pang, Xiaomeng Ding, Meng Tang
Summary: This study aims to explore the importance of reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress-induced autophagy in CdTe QDs toxicity, and the different cell outcomes in normal cells and cancer cells. The results showed that CdTe QDs induce ROS generation and prolonged ER stress in normal human liver cells (L02), leading to apoptosis. In contrast, CdTe QDs activate protective cellular autophagy in human liver cancer cells (HepG2 cells), preventing apoptosis.
ENVIRONMENTAL POLLUTION
(2023)
Article
Chemistry, Multidisciplinary
Feng Xiao, Yao Chen, Jie Qi, Qiaofeng Yao, Jianping Xie, Xingyu Jiang
Summary: In this study, a modified nanoparticle aggregate (AP(1)P(2)-PEG NCs) was designed for the treatment of unresectable solid liver tumors. The findings suggest that the nanoparticle aggregate can achieve the mutual promotion of autophagy and apoptosis in liver tumor cells, leading to a better anti-tumor effect.
ADVANCED MATERIALS
(2023)
Article
Multidisciplinary Sciences
Gunes Parlakgul, Ana Paula Arruda, Song Pang, Erika Cagampan, Nina Min, Ekin Guney, Grace Yankun Lee, Karen Inouye, Harald F. Hess, C. Shan Xu, Gokhan S. Hotamisligil
Summary: This study reveals the complex structural organization of organelles in liver tissue and highlights the significant alterations in obese mice. The functional importance of these structural changes on cellular and systemic metabolism is also demonstrated.
Review
Cell Biology
Srimanta Patra, Shankargouda Patil, Daniel J. J. Klionsky, Sujit K. K. Bhutia
Summary: Recent studies have shown that lysosomes, traditionally thought of as static garbage disposals, play a dynamic and multi-functional role in maintaining cellular homeostasis. Lysosomes sense cellular metabolic status and regulate the balance between catabolism and anabolism through signaling pathways, proteins, and transcription factors. Lysosomes also interact with other organelles and their positioning and motility are critical for cellular adaptation. Furthermore, lysosomes can orchestrate different cell death mechanisms to maintain cellular homeostasis, highlighting their central role as a signaling hub.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Physiology
Fulvio Reggiori, Maurizio Molinari
Summary: ER-phagy is the process of degrading portions of the endoplasmic reticulum (ER) within lysosomes or vacuoles. It plays a role in recycling cytoplasmic material and organelles, regulating ER size and activity, and removing potentially cytotoxic material. Dysfunctional ER-phagy is associated with specific human diseases and can be targeted by pathogens.
PHYSIOLOGICAL REVIEWS
(2022)
Article
Chemistry, Medicinal
Xueying Zhang, Zhaojiong Huo, Huiling Luan, Yihai Huang, Yanhui Shen, Liang Sheng, Jiangyu Liang, Feihua Wu
Summary: Scutellarin ameliorates hepatic lipid accumulation by enhancing autophagy and suppressing ER stress via the IRE1 alpha/XBP1 pathway.
PHYTOTHERAPY RESEARCH
(2022)
Article
Environmental Sciences
Yiqi Wang, Lian Duan, Xing Zhang, Yang Jiao, Ying Liu, Lingling Dai, Hong Yan
Summary: The study demonstrated that chronic exposure to ACR can impair motor skills, muscle strength, and coordination in rats, as well as damage the morphology of the cerebellum, leading to increased apoptosis and initiation of autophagy.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2021)
Article
Pharmacology & Pharmacy
Tingting Kong, Zhenxue He, Shuying Wang, Chunxin Jiang, Fei Zhu, Jingjing Gao, Liu Li, Yanping Wang, Qing Xie, Yunsen Li
Summary: The study found that DGA, a diterpenoid compound, has anti-glioma activity by inhibiting cell proliferation and inducing apoptosis. Its mechanism of action may be related to regulating endoplasmic reticulum stress and inhibiting the STAT3 signaling pathway. These findings suggest that DGA is a potential candidate for treating glioma.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Toxicology
Ye-Feng Wang, Rui-Xia Ma, Bin Zou, Jia Li, Yao Yao, Juan Li
Summary: Saikosaponin a (Ssa), an active ingredient of Radix Bupleuri, has severe hepatotoxicity. This study revealed that Ssa can induce endoplasmic reticulum stress and promote autophagy, leading to hepatocyte death.
TOXICOLOGY IN VITRO
(2023)
Review
Chemistry, Multidisciplinary
Yasaman Esmaeili, Zahra Yarjanli, Fatemeh Pakniya, Elham Bidram, Marek J. Los, Mehdi Eshraghi, Daniel J. Klionsky, Saeid Ghavami, Ali Zarrabi
Summary: Protein homeostasis is crucial for cell function, and disruption of the molecular mechanisms involved in this process may contribute to neurodegenerative diseases. Autophagy disruption, oxidative stress, and ER stress are the main molecular mechanisms underlying neurodegeneration, and they have synergistic effects on each other. Therefore, targeting the crosstalk between these pathways may play a critical role in healing neurodegenerative diseases.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Tingting Wang, Guangxu Xiao, Qianglan Lu, Yue Zhou, Siyu Wang, Xiaoyang Liang, Yilin Song, Min Xu, Yan Zhu, Nan Li
Summary: This study proposes an innovative pharmacological strategy to enhance autophagy dysfunction by combining endoplasmic reticulum stress and lysosomal impairment. The results show that the synthesized nanobullets exhibit excellent therapeutic efficacy by inducing ER stress and impairing lysosomes, leading to autophagy dysfunction. This research provides a promising therapeutic nanoagent for effective tumor therapy.
Article
Chemistry, Multidisciplinary
Yuping Zhao, Hyeong Seok Kim, Xiang Zou, Ling Huang, Xing Liang, Zihong Li, Jong Seung Kim, Weiying Lin
Summary: This study proposed a new strategy to investigate the interaction regulatory mechanisms between endoplasmic reticulum and autophagosomes by developing dual fluorescence lifetime probes localized to these two organelles. The research revealed that motile autophagosomes at the tips of endoplasmic reticulum drive the growth and sliding of ER tubules, ER reticulate tubules form a three-way junction centered on autophagosomes, and ER autophagy serves as a cell damage index during drug-induced apoptosis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Yoshito Minami, Atsushi Hoshino, Yusuke Higuchi, Masahide Hamaguchi, Yusaku Kaneko, Yuhei Kirita, Shunta Taminishi, Toshiyuki Nishiji, Akiyuki Taruno, Michiaki Fukui, Zoltan Arany, Satoaki Matoba
Summary: Nonalcoholic steatohepatitis (NASH) is caused by lipid accumulation in the liver, leading to inflammation and fibrosis. The authors use lipophagy activators to reduce lipid accumulation and demonstrate that this can prevent disease progression in a mouse model of NASH.
NATURE COMMUNICATIONS
(2023)
Article
Gastroenterology & Hepatology
Sandra Torres, Cristina Ortiz, Nadine Bachtler, Wenyi Gu, Leon D. Gruenewald, Nico Kraus, Robert Schierwagen, Christoph Hieber, Caroline Meier, Olaf Tyc, Maximilian Joseph Brol, Frank Erhard Uschner, Bart Nijmeijer, Christoph Welsch, Marie-Luise Berres, Carmen Garcia-Ruiz, Jose Carlos Fernandez-Checa, Christian Trautwein, Thomas J. Vogl, Stefan Zeuzem, Jonel Trebicka, Sabine Klein
Summary: The JAK2 inhibitor pacritinib showed promising antifibrotic effects on hepatic stellate cells and two animal models of liver fibrosis, suggesting its potential for treating alcoholic and nonalcoholic liver fibrosis in human pathology.
Editorial Material
Gastroenterology & Hepatology
Benjamin H. H. Mullish, Laura Martinez-Gili, Jessica R. R. Allegretti
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Alma M. Astudillo, Maria A. Balboa, Jesus Balsinde
Summary: Lipid homeostasis perturbations and conditions favoring oxidative stress are important in the inflammatory response. Recent research has focused on lipid signaling in oxidative stress-mediated responses and inflammation, including phagocytosis and ferroptosis. The synthesis of oxygenated metabolites of arachidonic acid and other polyunsaturated fatty acids is a common event in these responses. Advances in this area highlight the importance of compartmentalization of enzymes and lipid substrates in shaping the appropriate response. Understanding the role of specific enzymes, such as iPLA213, in oxidative stress and inflammation may lead to new therapeutic interventions.
PROGRESS IN LIPID RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Cristina Alarcon-Vila, Naroa Insausti-Urkia, Sandra Torres, Paula Segales-Rovira, Laura Conde de la Rosa, Susana Nunez, Raquel Fucho, Jose C. Fernandez-Checa, Carmen Garcia-Ruiz
Summary: Alcoholic (ASH) and nonalcoholic (NASH) steatohepatitis are advanced stages of fatty liver disease. Methionine adenosyltransferase 1A (MAT1A) plays a key role in hepatic methionine metabolism and germline Mat1a deletion in mice promotes NASH. Acid sphingomyelinase (ASMase) triggers hepatocellular apoptosis and liver fibrosis and has been shown to downregulate MAT1A expression in the context of fulminant liver failure. Disruption of methionine metabolism sensitizes to steatohepatitis by ASMase activation via decreased SAM/SAH.
Editorial Material
Gastroenterology & Hepatology
Jose C. Fernandez-Checa, Sandra Torres, Carmen Garcia-Ruiz
JOURNAL OF HEPATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Leire Goicoechea, Laura Conde de la Rosa, Sandra Torres, Carmen Garcia-Ruiz, Jose C. Fernandez-Checa
Summary: Cholesterol is a crucial component of cell membrane bilayers and has important physiological roles in mitochondria and its metabolism. Excessive mitochondrial cholesterol can lead to oxidative stress, cell death, and the development of various diseases.
Article
Gastroenterology & Hepatology
Laura Martinez-Gili, Alexandros Pechlivanis, Julie A. K. McDonald, Sofina Begum, Jonathan Badrock, Jessica K. Dyson, Rebecca Jones, Gideon Hirschfield, Stephen D. Ryder, Richard Sandford, Simon Rushbrook, Douglas Thorburn, Simon D. Taylor-Robinson, Mary M. E. Crossey, Julian R. Marchesi, George Mells, Elaine Holmes, David Jones
Summary: A study on patients with primary biliary cholangitis (PBC) showed that there is variation in response to ursodeoxycholic acid (UDCA) treatment. Responders exhibited high levels of secondary and tertiary bile acids, while non-responders had lower urinary bile acid levels and higher levels of 12-dehydrocholic acid. Additionally, non-responders showed lower gut microbiota diversity and lower capacity for bile acid deconjugation.
Article
Biochemistry & Molecular Biology
Nagore de Pablo, Clara Meana, Javier Martinez-Garcia, Pablo Martinez-Vicente, Manuel Albert, Susana Guerra, Ana Angulo, Jesus Balsinde, Maria A. Balboa
Summary: This study reveals that interferons regulate the expression of lipin-2, which can inhibit viral replication and regulate inflammation. Furthermore, LPIN2 expression levels are negatively correlated with the severity of COVID-19.
Article
Biochemistry & Molecular Biology
Raquel Fucho, Estel Solsona-Vilarrasa, Sandra Torres, Susana Nunez, Naroa Insausti-Urkia, Albert Edo, Maria Calvo, Anna Bosch, Gemma Martin, Carlos Enrich, Carmen Garcia-Ruiz, Jose C. Fernandez-Checa
Summary: In this study, we found that StARD1 is predominantly expressed in the perivenous zone of the liver in patients with chronic alcoholic liver disease. This zonal-dependent expression of StARD1 results in the accumulation of cholesterol and increased lipid peroxidation in mitochondria, leading to liver cell injury. We also observed changes in mitochondrial morphology and function following alcohol intake. These findings highlight the importance of StARD1 in the pathogenesis of alcoholic liver disease.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Bertrand Routy, John G. Lenehan, Wilson H. Miller, Rahima Jamal, Meriem Messaoudene, Brendan A. Daisley, Cecilia Hes, Kait F. Al, Laura Martinez-Gili, Michal Puncochar, Scott Ernst, Diane Logan, Karl Belanger, Khashayar Esfahani, Corentin Richard, Marina Ninkov, Gianmarco Piccinno, Federica Armanini, Federica Pinto, Mithunah Krishnamoorthy, Rene Figueredo, Pamela Thebault, Panteleimon Takis, Jamie Magrill, LeeAnn Ramsay, Lisa Derosa, Julian R. Marchesi, Seema Nair Parvathy, Arielle Elkrief, Ian R. Watson, Rejean Lapointe, Nicola Segata, S. M. Mansour Haeryfar, Benjamin H. Mullish, Michael S. Silverman, Jeremy P. Burton, Saman Maleki Vareki
Summary: A multicenter phase I trial evaluated the safety and efficacy of fecal microbiota transplantation (FMT) combined with PD-1 inhibitors in first-line treatment of advanced melanoma. The results showed that FMT from healthy donors was safe and demonstrated potential antitumor effects in this setting.
Correction
Biochemistry & Molecular Biology
Bertrand Routy, John G. Lenehan, Wilson H. Miller Jr, Rahima Jamal, Meriem Messaoudene, Brendan A. Daisley, Cecilia Hes, Kait F. Al, Laura Martinez-Gili, Michal Puncochar, Scott Ernst, Diane Logan, Karl Belanger, Khashayar Esfahani, Corentin Richard, Marina Ninkov, Gianmarco Piccinno, Federica Armanini, Federica Pinto, Mithunah Krishnamoorthy, Rene Figueredo, Pamela Thebault, Panteleimon Takis, Jamie Magrill, Leeann Ramsay, Lisa Derosa, Julian R. Marchesi, Seema Nair Parvathy, Arielle Elkrief, Ian R. Watson, Rejean Lapointe, Nicola Segata, S. M. Mansour Haeryfar, Benjamin H. Mullish, Michael S. Silverman, Jeremy P. Burton, Saman Maleki Vareki
Article
Gastroenterology & Hepatology
Irma Garcia-Martinez, Rosa Alen, Laura Pereira, Adrian Povo-Retana, Alma M. Astudillo, Ana B. Hitos, Isabel Gomez-Hurtado, Eduardo Lopez-Collazo, Lisardo Bosca, Ruben Frances, Ignacio Lizasoain, Maria Angeles Moro, Jesus Balsinde, Manuel Izquierdo, Angela M. Valverde
Summary: This study reveals that small extracellular vesicles (sEV) released by hepatocytes under NAFLD conditions induce liver inflammation and insulin resistance in hepatocytes through paracrine hepatocyte-macrophage-hepatocyte crosstalk. These sEV act as transporters of saturated fatty acids (SFAs) and potent inducers of liver inflammation. Liver inflammation mediated by sEV can be attenuated by inhibiting Toll-like receptor-4 (TLR4). Evidence of macrophage-hepatocyte interactome was also found in patients with NAFLD, highlighting the relevance of sEV in SFAs-mediated lipotoxicity in NAFLD.
Article
Biochemistry & Molecular Biology
Patricia Monge, Alma M. Astudillo, Laura Pereira, Maria A. Balboa, Jesus Balsinde
Summary: This study investigates the incorporation and redistribution of DHA in mouse macrophages. DHA is initially taken up by choline glycerophospholipids and transferred to ethanolamine glycerophospholipids through prolonged incubation. Mass spectrometry analysis reveals a high abundance of DHA in ether phospholipids. Stimulation of macrophages leads to decreases in DHA-containing PC and PI species, while an unusual DHA-containing species, PI(20:4/22:6), markedly increases.
Article
Cell Biology
Emma Barroso, Marta Diaz, Ana Cristina Reguera, Mona Peyman, Jesus Balsinde, Javier Jurado-Aguilar, Meijian Zhang, Adel Rostami, Xavier Palomer, Lourdes Ibanez, Manuel Vazquez-Carrera
Summary: Placentas from newborns that are SGA display multiple pathological characteristics, and placental amino acid transport regulated by mTOR plays a key role in fetal growth. The effects of ER stress on the mTOR pathway and amino acid transporters are not well understood.
CELL COMMUNICATION AND SIGNALING
(2023)
Meeting Abstract
Gastroenterology & Hepatology
Roberta Forlano, Laura Martinez-Gili, Jesus Miguens Blanco, Charlotte Skinner, Mark Thursz, Julian Marchesi
JOURNAL OF HEPATOLOGY
(2023)