Article
Multidisciplinary Sciences
Yeawon Kim, Chuang Li, Chenjian Gu, Yili Fang, Eric Tycksen, Anuradhika Puri, Terri A. Pietka, Jothilingam Sivapackiam, Kendrah Kidd, Sun-Ji Park, Bryce G. Johnson, Stanislav Kmoch, Jeremy S. Duffield, Anthony J. Bleyer, Meredith E. Jackrel, Fumihiko Urano, Vijay Sharma, Maria Lindahl, Ying Maggie Chen
Summary: Research shows that mesencephalic astrocyte-derived neurotrophic factor can improve defective autophagy/mitophagy and decrease renal scarring in ADTKD.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ann Cuypers, Isabeau Vanbuel, Verena Iven, Kris Kunnen, Stephanie Vandionant, Michiel Huybrechts, Sophie Hendrix
Summary: Cadmium is a toxic compound that is harmful to human health and efforts are needed to remediate Cd-polluted soils. It is important to understand the molecular mechanisms underlying Cd stress responses in plants and develop strategies for economic validation of these soils.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Imadeddin Hijazi, Emily Wang, Michelle Orozco, Sarah Pelton, Amy Chang
Summary: Endoplasmic reticulum stress (ERS) occurs when cellular demand for protein folding exceeds the capacity of the organelle. Adaptation and cell survival in response to ERS require the contribution of mitochondria and peroxisomes. Our study in yeast shows that during ERS, both mitochondrial respiration and peroxisome abundance increase to promote an adaptive response.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Olena Odnokoz, Noah Earland, Marziyeh Badinloo, Vladimir I. Klichko, Judith Benes, William C. Orr, Svetlana N. Radyuk
Summary: Aberrant immune responses and chronic inflammation can increase health risks and promote premature aging. Peroxiredoxins (Prxs) play a critical role in maintaining cellular redox homeostasis and regulating the immune response. The activity of mitochondrial Prxs in the intestinal epithelium is important for preventing intestinal barrier dysfunction, systemic inflammation, and premature aging.
Article
Food Science & Technology
Ziping Yu, Zhao Zhang, Xuancheng Zhang, Junduo Bao, Hualin Li, Jiapei Yu, Ning Shi, Fulong Nan, Liang Cao, Chenghui Li, Wei Wang
Summary: This study found that 4-octyl itaconate (4-OI) can impede the progression of osteoarthritis (OA) by promoting the expression of SIRT1 gene, thus inhibiting apoptosis, extracellular matrix degeneration, mitochondrial dysfunction, endoplasmic reticulum stress, and excessive accumulation of reactive oxygen species.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Developmental Biology
Lucy A. Bartho, Daniel R. McKeating, Natalie J. Hannan, Tu'uhevaha J. Kaitu'u-Lino, Anthony Perkins
Summary: This study aimed to investigate the correlation between genes related to mitochondria, endoplasmic reticulum (ER), and cellular senescence in placentae affected by pregnancy complications. The findings suggest that genes associated with mitochondrial dynamics and aging undergo changes in placentae affected by pregnancy pathologies. The TOMM20/PARK2 ratio may be a promising marker for distinguishing between healthy and unhealthy placental tissue.
MOLECULAR HUMAN REPRODUCTION
(2022)
Article
Chemistry, Multidisciplinary
Hong-Gui Xu, Margot Schikora, Miroslav Sisa, Steffen Daum, Insa Klemt, Christina Janko, Christoph Alexiou, Galyna Bila, Rostyslav Bilyy, Wenjie Gong, Michael Schmitt, Leopold Sellner, Andriy Mokhir
Summary: Novel ER-targeted prodrugs have been developed with activation only in cancer cells, demonstrating anticancer efficacy and cancer cell specificity. These prodrugs induce ER stress, attenuate mitochondrial membrane potential, and generate mitochondrial ROS leading to cell death via necrosis. Activation of the new prodrugs has also been demonstrated in the Nemeth-Kellner lymphoma murine model.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Neurosciences
Cui Wang, Xiaoyi Wang, Yinyin Xie, Tingting Peng, Yongfeng Wang, Nan Li, Xiangbo Huang, Xiaomei Hu, Nanchang Xie
Summary: This study demonstrated that ATF5 can attenuate low-magnesium-induced endoplasmic reticulum stress (ERS) by preventing the accumulation of mitochondrial reactive oxygen species (ROS), thereby rescuing neuronal cells from apoptosis.
Article
Plant Sciences
Mengqian Luo, Kai Ching Law, Yilin He, Ka Kit Chung, Muk Kuen Po, Lanlan Feng, Kin Pan Chung, Caiji Gao, Xiaohong Zhuang, Liwen Jiang
Summary: This study reveals the role of AUTOPHAGY-RELATED2 in coordinating the trafficking of ATG18a and ATG9 to mediate autophagosome closure in Arabidopsis. Under normal conditions, ATG2 is essential for the transport of ATG18a and ATG9, and its depletion leads to unclosed autophagosome structures.
Article
Oncology
Hassan Choucair, Md Khalilur Rahman, Balasubrahmanyam Umashankar, Yassir Al-Zubaidi, Kirsi Bourget, Yongjuan Chen, Colin Dunstan, Tristan Rawling, Michael Murray
Summary: CTU is a novel class of mitochondrion-targeted agents that induce cancer cell death by disrupting the inner mitochondrial membrane, inhibiting complex III, and increasing ROS production. The mechanism of action involves activation of the ER-stress pathway by mitochondrion-derived ROS, leading to NOXA induction and OMM disruption, ultimately resulting in apoptosis.
Article
Plant Sciences
Chien-Liang Lin, Chung- Yu, Tzong-Huei Lee, Jimmy Ming -Jung Chuang, Kuang-Fen Han, Chang-Shen Lin, Wan-Ping Huang, Jeff Yi-Fu Chen, Chung-Yi Chen, Mei-Ying Lin, Chien-Hsing Lee
Summary: This study demonstrated that plumbagin (PG), a natural compound isolated from Plumbago zeylanica L, exhibits anticancer effects against drug-resistant oral cancer cells by reducing cell viability, inducing apoptosis, and triggering intracellular and mitochondrial ROS generation, leading to mitochondrial dysfunction and endoplasmic reticulum stress. In addition, the inhibition of ROS abolished the effects of PG on cell viability, apoptosis, and ER stress.
Article
Pharmacology & Pharmacy
Md Khalilur Rahman, Balasubrahmanyam Umashankar, Hassan Choucair, Curtis Pazderka, Kirsi Bourget, Yongjuan Chen, Colin R. Dunstan, Tristan Rawling, Michael Murray
Summary: Mitochondria in tumor cells are different from normal cells and can be targeted for new anticancer agents. The aryl-ureido fatty acid CTU is a prototype of mitochondrion-targeted agents that kill cancer cells by increasing ROS production, activating ER-stress, and promoting apoptosis. However, high doses of CTU are required for in vivo anti-tumor activity, so new strategies are needed to enhance its effectiveness. In this study, a novel aryl-urea called 3-thiaCTU was developed and found to be more active than CTU in promoting cancer cell killing mechanisms in vitro and in mice carrying tumor xenografts. These findings suggest that 3-thiaCTU could be a promising candidate for development as a novel anticancer agent.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Fawzi Khoder-Agha, Thomas Kietzmann
Summary: Reactive oxygen species (ROS) and glycans play crucial roles in cells, both dynamically responding to stressors to maintain cellular balance. The delicate balance of redox potential and glycan biosynthesis vitality are essential for cell survival.
Review
Biochemistry & Molecular Biology
Gideon Ong, Susan E. Logue
Summary: Oxidative stress is caused by an imbalance in cellular redox state due to the accumulation of reactive oxygen species (ROS). It can lead to negative effects such as damage to biological macromolecules and disruption of organelle function. The unfolded protein response (UPR), a stress response initiated by cells to combat endoplasmic reticulum (ER) stress, is well characterized, but its response and influence on oxidative stress are less defined. This review evaluates the interplay between oxidative stress, ER stress, and UPR signaling networks, particularly focusing on how UPR signaling mediators can influence antioxidant responses.
Article
Biochemistry & Molecular Biology
Zohar Shpilt, Naomi Melamed-Book, Edit Y. Tshuva
Summary: The cellular mechanism of PhenolaTi, a promising Ti(IV) anticancer complex, was investigated and found to be related to ER stress, leading to the formation of mitochondrial ROS and hypoxia. Unlike cisplatin, PhenolaTi has a distinct mechanism of action, stability, and favorable anticancer properties, making it a strong candidate for chemotherapy.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2023)
Article
Cardiac & Cardiovascular Systems
Chiara Ruocco, Maurizio Ragni, Laura Tedesco, Agnese Segala, Maurizio Servili, Gabriele Riccardi, Michele O. Carruba, Alessandra Valerio, Enzo Nisoli, Francesco Visioli
Summary: The study investigates the effects of replacing saturated fatty acids with extra-virgin olive oil on cardiometabolic and hepatic outcomes.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Article
Pharmacology & Pharmacy
Sissi Dolci, Loris Mannino, Emanuela Bottani, Alessandra Campanelli, Marzia Di Chio, Stefania Zorzin, Giulia D'Arrigo, Alessia Amenta, Agnese Segala, Giuseppe Paglia, Vanna Denti, Guido Fumagalli, Enzo Nisoli, Alessandra Valerio, Claudia Verderio, Giuseppe Martano, Francesco Bifari, Ilaria Decimo
Summary: Rewiring cellular metabolism to recover oxidative metabolism may be an innovative therapeutic strategy for the treatment of spinal cord injury (SCI). In this study, oral administration of metabolic precursors enhanced spinal cord oxidative metabolism, activated the mTORC1 anabolic pathway, increased mitochondrial mass and ROS defense, effectively preventing neural cell apoptosis. These molecular and histological modifications ultimately led to a significant improvement in motor functions.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Maurizio Ragni, Chiara Ruocco, Laura Tedesco, Michele O. Carruba, Alessandra Valerio, Enzo Nisoli
Summary: The study demonstrates that dietary intervention can reverse the metabolic inflexibility of tumors, promote tumor cell death, and highlight the potential of specific amino acid mixtures in cancer therapy.
MOLECULAR METABOLISM
(2022)
Article
Cardiac & Cardiovascular Systems
Maurizio Ragni, Carolina Magdalen Greco, Arianna Felicetta, Shuxun Vincent Ren, Paolo Kunderfranco, Chiara Ruocco, Pierluigi Carullo, Veronica Larcher, Laura Tedesco, Ilenia Severi, Antonio Giordano, Saverio Cinti, Alessandra Valerio, Haipeng Sun, Yibin Wang, Chen Gao, Gianluigi Condorelli, Enzo Nisoli
Summary: A designer diet with essential amino acids substituted for protein has shown remarkable therapeutic effects on heart failure, improving glucose metabolism and mitochondrial fuel oxidation.
CARDIOVASCULAR RESEARCH
(2023)
Article
Geriatrics & Gerontology
Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Robertina Giacconi, Maurizio Cardelli, Francesco Piacenza, Fiorenza Orlando, Agnese Segala, Alessandra Valerio, Enzo Nisoli, Dario Brunetti, Annibale Puca, Federico Boschi, Carlo Gaetano, Alessia Mongelli, Fabrizia Lattanzio, Mauro Provinciali, Marco Malavolta
Summary: Frailty is an age-related condition characterized by functional decline, vulnerability to stressors, and adverse health outcomes. Two validated measurements, frailty phenotype (FP) and clinical frailty index (CFI), have limitations in identifying frail mice. In this study, a physical function score (PFS) was developed as a continuous variable integrating the criteria of FP to reduce misclassification of frailty. The PFS, along with CFI, was used to calculate a vitality score (VS) in aging mice, which showed higher association with mortality and correlated with biomarkers linked to senescent cells and the epigenetic clock. This non-invasive assessment and the VS may improve frailty identification, reduce sample size, and evaluate interventions for age-related diseases in geriatric animals.
Article
Medicine, Research & Experimental
Riccardo Dalle Grave, Simona Calugi, Chiara Ruocco, Mirko Chimini, Agnese Segala, Maurizio Ragni, Michele Carruba, Alessandra Valerio, Enzo Nisoli
Summary: This study aims to evaluate the efficacy of supplementing a mixture of essential amino acids (EAA) and tricarboxylic acid (TCA) cycle intermediates in increasing lean body mass (LBM) and improving physical and psychological outcomes in patients with anorexia nervosa (AN) who undergo specialized intensive treatment for eating disorders. The results of this study will provide insights on the effectiveness of supplementation with EAA and TCA intermediates in improving LBM and other important physical and psychological outcomes in AN patients who regain weight with specialized intensive treatment.
Article
Cardiac & Cardiovascular Systems
Alexis Elias Malavazos, Gianluca Iacobellis, Elena Dozio, Sara Basilico, Angelica Di Vincenzo, Carola Dubini, Lorenzo Menicanti, Elena Vianello, Chiara Meregalli, Chiara Ruocco, Maurizio Ragni, Francesco Secchi, Pietro Spagnolo, Serenella Castelvecchio, Lelio Morricone, Silvio Buscemi, Antonio Giordano, Jeffrey J. Goldberger, Michele Carruba, Saverio Cinti, Massimiliano Marco Corsi Romanelli, Enzo Nisoli
Summary: Human epicardial adipose tissue (EAT) is a unique and multifunctional fat compartment of the heart that can directly interact with the myocardium. It plays a key role in the development and progression of coronary artery disease, atrial fibrillation, and heart failure. Targeting EAT through G-protein-coupled receptors, such as GLP-1R agonists, can be a novel therapeutic approach.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2023)
Article
Neurosciences
Maurizio Ragni, Francesca Fenaroli, Chiara Ruocco, Agnese Segala, Giuseppe D'Antona, Enzo Nisoli, Alessandra Valerio
Summary: Mitochondrial dysfunction is involved in aging and neurodegenerative diseases, including ischemic stroke. Non-pharmacological interventions like exercise can prevent stroke, but they are challenging for older individuals. This study suggests that dietary supplementation with a balanced essential amino acid mixture (BCAAem) can mimic the effects of exercise on brain mitochondria and prevent neurodegeneration. BCAAem treatment directly promotes mitochondrial biogenesis and protects cortical neurons from ischemic damage. The mTOR and eNOS signaling pathways are involved in the effects of BCAAem. It is proposed that BCAAem supplementation can be an alternative to exercise in preventing brain mitochondrial dysfunction and aiding recovery after cerebral ischemia.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Maurizio Ragni, Luca Canciani, Letizia Spataro, Chiara Ruocco, Alessandra Valerio, Enzo Nisoli
Summary: The skin is greatly affected by the aging process, and nutritional approaches that promote ECM gene expression may help counteract skin aging. This study found that a formulation enriched with tricarboxylic acid intermediates stimulated ECM gene expression, and protected against oxidative damage. These findings suggest that this non-pharmacological approach could be used to combat skin aging.
Article
Pharmacology & Pharmacy
Chiara Ruocco, Alexis Elias Malavazos, Maurizio Ragni, Michele O. Carruba, Alessandra Valerio, Gianluca Iacobellis, Enzo Nisoli
Summary: Adaptive thermogenesis refers to the heat production by muscle contractions or brown adipose tissue in response to external stimuli. Brown adipose tissue and beige fat communicate with peripheral organs and the brain through secretory and absorption processes, and have potential therapeutic applications in obesity-related disorders.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Medicine, General & Internal
Amelia Brunani, Raffaella Cancello, Michele Gobbi, Elisa Lucchetti, Giulia Di Guglielmo, Sabrina Maestrini, Stefania Cattaldo, Paolo Pitera, Chiara Ruocco, Alessandra Milesi, Alessandra Valerio, Paolo Capodaglio, Enzo Nisoli
Summary: This study aimed to assess the impact of protein or amino acid supplements on muscle mass loss in middle-aged men. The results showed that the PD-E07 supplement group had a notable increase in muscle mass compared to the control group, while the protein and BCAA supplement groups did not exhibit a significant difference. Therefore, amino acid-based supplements may effectively mitigate the loss of muscle mass during weight reduction.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Emirena Garrafa, Agnese Segala, Marika Vezzoli, Emanuela Bottani, Barbara Zanini, Alice Vetturi, Renata Bracale, Chiara Ricci, Alessandra Valerio
Summary: Non-alcoholic fatty liver disease (NAFLD) is a global health emergency due to its high prevalence and lack of specific therapies. This study found that mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) is associated with NAFLD, as indicated by reduced basal respiration, ATP-linked respiration, maximal respiration, and spare respiratory capacity in NAFLD patients compared to control subjects. These mitochondrial respiratory parameters were correlated with triglycerides, fasting insulin levels, IL-6 levels, HDL-cholesterol level, and fatty liver index, suggesting their potential as predictive biomarkers for NAFLD.
Review
Geriatrics & Gerontology
Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Robertina Giacconi, Francesco Piacenza, Maurizio Cardelli, Dario Brunetti, Agnese Segala, Alessandra Valerio, Enzo Nisoli, Fabrizia Lattanzio, Mauro Provinciali, Marco Malavolta
Summary: This study provides a comprehensive evaluation of the role of senescent cells in driving inflammation and frailty. The results indicate that the burden of senescent cells related to musculoskeletal and cerebral health has the strongest causal link to frailty. These findings are important for understanding the role of cellular senescence in frailty and developing personalized therapies.
