Article
Chemistry, Multidisciplinary
Zhenqi Liu, Geng Qin, Jie Yang, Wenjie Wang, Wenting Zhang, Boxun Lu, Jinsong Ren, Xiaogang Qu
Summary: Researchers have developed a biochemical method called mito-ATTECs to modulate mitophagy by directly interacting with LC3 on mitochondrial membranes. This approach bypasses the detrimental effects of traditional inducers on mitochondrial membrane integrity and can be used to investigate the physiological roles of mitophagy.
Article
Cell Biology
Jery Joy, Lara Barrio, Celia Santos-Tapia, Daniela Romao, Nikolaos Nikiforos Giakoumakis, Marta Clemente-Ruiz, Marco Milan
Summary: Aneuploidy, an unbalanced number of chromosomes, leads to cellular senescence with the activation of protein quality control mechanisms and compromised mitophagy. The role of c-Jun N-terminal kinase (JNK) in driving senescence as a consequence of dysfunctional mitochondria and ROS is uncovered. Activating protein quality control mechanisms and mitophagy can mitigate the deleterious effects of aneuploidy, and senescence plays a crucial role in proteostasis and compensatory proliferation for tissue repair.
DEVELOPMENTAL CELL
(2021)
Article
Multidisciplinary Sciences
Jaskaren Kohli, Chen Ge, Eleni Fitsiou, Miriam Doepner, Simone M. Brandenburg, William J. Faller, Todd W. Ridky, Marco Demaria
Summary: Research shows that senescent melanocytes in culture and nevi express high levels of the anti-apoptotic protein BCL-W, but remain insensitive to the pan-BCL-2 inhibitor ABT-263. Resistance to ABT-263 is driven by mTOR-mediated enhanced translation of another anti-apoptotic protein, MCL-1. The combination of ABT-263 and MCL-1 inhibitors results in synthetic lethality to senescent melanocytes, with topical application sufficient to eliminate nevi.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Woonghee Lee, Garam An, Hahyun Park, Whasun Lim, Gwonhwa Song
Summary: DFB, a common benzoylurea insecticide, shows cytotoxic effects on bovine mammary epithelial cells (MAC-T), leading to apoptosis through ROS generation and mitochondrial dysfunction.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Rongqing Pan, Jeremy Ryan, Deng Pan, Kai W. Wucherpfennig, Anthony Letai
Summary: The mitochondrial apoptosis pathway is crucial for efficient NK cell killing, with pre-activated NK cells demonstrating resistance to BH3 mimetics. Combining BH3 mimetics with NK cells synergistically kills cancer cells and inhibits tumor growth in vivo.
Article
Oncology
Ruth Soler-Agesta, Joaquin Marco-Brualla, Martha Minjarez-Saenz, Christina Y. Yim, Marta Martinez-Julvez, Matthew R. Price, Raquel Moreno-Loshuertos, Tyler D. Ames, Jose Jimeno, Alberto Anel
Summary: PT-112 was found to induce immunogenic cell death in tumor cells, with increased sensitivity in cells with mitochondrial dysfunction and reliance on glycolysis. The mechanism of cell death induced by PT-112 involves autophagy and accumulation of mitochondrial reactive oxygen species. The findings suggest a potential relationship between stress response and immunogenic cell death in cancer cells.
Review
Biotechnology & Applied Microbiology
Kamyar Hadian, Brent R. R. Stockwell
Summary: This article introduces the regulation of non-apoptotic cell death, such as necroptosis, pyroptosis, parthanatos, and ferroptosis, and provides an update on the development of small-molecule inhibitors targeting these pathways. Cell death is critical for the development and homeostasis of multicellular organisms, and dysregulation can lead to various diseases. Recent research has uncovered regulated forms of necrosis that are associated with degenerative diseases, inflammation, and cancer. Understanding these pathways offers new opportunities for therapeutic targeting.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Chemistry, Multidisciplinary
Liqiang Zhou, Caihong Dong, Li Ding, Wei Feng, Luodan Yu, Xinwu Cui, Yu Chen
Summary: This study developed a nano-sensitizer system that simultaneously encapsulated ferumoxytol to induce dual ferroptosis/apoptosis pathways by SDT. Ferumoxytol delivers excessive iron into cancer cells, leading to tumor metabolic rewiring and enhanced sensitivity to SDT-induced cell apoptosis. The modulation of ferroptosis checkpoints through ferritinophagy by SDT improves ferroptosis sensitivity and achieves synergistic tumor suppression.
Review
Pharmacology & Pharmacy
Hao Yang, Shan Xu, Lidan Tang, Jinhong Gong, Hufeng Fang, Jifu Wei, Dan Su
Summary: This review summarizes the current status of research on the molecular mechanisms and targets of quercetin-mediated non-apoptotic cell death modes.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katia Cosentino, Vanessa Hertlein, Andreas Jenner, Timo Dellmann, Milos Gojkovic, Aida Pena-Blanco, Shashank Dadsena, Noel Wajngarten, John S. H. Danial, Jervis Vermal Thevathasan, Markus Mund, Jonas Ries, Ana J. Garcia-Saez
Summary: BAX and BAK are important regulators of apoptosis and play a role in the formation of apoptotic pores. BAK has faster kinetics in forming smaller structures and can accelerate the assembly of BAX. BAX and BAK regulate each other during the formation of apoptotic pores, which affects the release kinetics of mitochondrial components and the activation kinetics of the cGAS/STING pathway.
Article
Biochemistry & Molecular Biology
Chang Ying, Chengmeng Jin, Siying Zeng, Ming Chao, Xun Hu
Summary: This study reveals that interfering cellular pH may provide a valuable approach to treat cancer.
Article
Biochemistry & Molecular Biology
Werner J. Geldenhuys, Debbie Piktel, Javohn C. Moore, Stephanie L. Rellick, Ethan Meadows, Mark Pinti, John M. Hollander, Amanda G. Ammer, Karen H. Martin, Laura F. Gibson
Summary: B-cell acute lymphoblastic leukemia (ALL) affects both pediatric and adult patients. Resistant tumor cells contribute to minimal residual disease, leading to poor clinical outcomes in some patients. Targeting mitochondrial oxidative phosphorylation (OXPHOS) in the treatment of refractory leukemic cells is a potential novel approach. In this study, knockout of mitoNEET in REH leukemic cells led to changes in mitochondrial function and ultrastructure, decreased OXPHOS capacity, increased reactive oxygen species, and decreased proliferation when exposed to cytarabine.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Oncology
Yingjie Qing, Yongjian Guo, Qinwen Zhao, Po Hu, Hui Li, Xiaoxuan Yu, Mengyuan Zhu, Hongzheng Wang, Zhanyu Wang, Jingyan Xu, Qinglong Guo, Hui Hui
Summary: A new lysosomotropic compound, V8, has been found to induce lysosomal-dependent cell death and effectively control the growth of T cell malignancies. V8 binds to heat shock protein 70 (HSP70), inhibits the activity of acid sphingomyelinase (ASM), and leads to disturbances in lipid metabolism, instability of lysosomal membrane, and leakage of cathepsin B and D, ultimately causing cell death. This study highlights the potential of targeting the lysosomal HSP70-ASM axis for T cell malignancy therapy.
CLINICAL AND TRANSLATIONAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Zhou Zeng, Mengling You, Cong Fan, Rong Rong, Haibo Li, Xiaobo Xia
Summary: Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell loss and visual field defects. High intraocular pressure (ph-IOP) is an important risk factor for glaucoma and triggers specific molecular pathways leading to retinal ganglion cell death. This study investigates the role of the ERK1/2-Drp1-reactive oxygen species (ROS) axis in retinal ganglion cell death and the relationship between Drp1-mediated mitochondrial dynamics and PANoptosis in ph-IOP injury. The findings suggest that inhibiting the ERK1/2-Drp1-ROS pathway may be a potential therapeutic strategy for ph-IOP-induced injuries.
Article
Chemistry, Analytical
Emma B. Hartnett, Mengli Zhou, Yi-Nan Gong, Yu-Chih Chen
Summary: The study developed a label-free method to classify cell death status using machine learning and image processing. It enables the precise categorization of live, apoptotic, and necrotic cells and allows for tracking the time dynamics of cell death process, enhancing the understanding of cell death regulation at the molecular level.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Markus Kwik, Stefan Hainzl, Jan Oppelt, Boris Tichy, Ulrich Koller, Emanuele Bernardinelli, Markus Steiner, Greta Zara, Charity Nofziger, Serge Weis, Markus Paulmichl, Silvia Dossena, Wolfgang Patsch, Selma M. Soyal
Summary: The study focuses on the transcriptional regulator PGC-1 alpha, with specific isoforms expressed in the CNS having distinct functional differences compared to reference proteins. Activation of the CNS promoter led to more differentially expressed genes compared to the reference promoter, while alternative exon usage was similar. The distinct N-terminal regions and shared downstream regions of PGC-1 alpha isoforms influence exon usage of multiple genes, with implications for neurodegenerative diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Physiology
Alessia Remigante, Sara Spinelli, Michael Pusch, Antonio Sarikas, Rossana Morabito, Angela Marino, Silvia Dossena
Summary: Bicarbonate, a major anion in mammalian tissues and fluids, plays a critical role in cell and systemic pH homeostasis and is involved in transporting ions and substrates across cell membranes. Chloride/bicarbonate exchangers, abundant in erythrocytes and epithelial cells, are particularly susceptible to oxidative stress. This review focuses on the physiological functions and pathophysiological changes of Cl-/HCO3- exchangers belonging to the SLC4 and SLC26 superfamilies in relation to oxidative stress.
Article
Biochemistry & Molecular Biology
Gergely Pallag, Sara Nazarian, Dora Ravasz, David Bui, Timea Komlodi, Carolina Doerrier, Erich Gnaiger, Thomas N. Seyfried, Christos Chinopoulos
Summary: This study demonstrates that ProDH-directed proline catabolism can generate sufficient CIII and CIV proton pumping to support ATP production by the F1FO-ATPase even under CI inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Alessia Remigante, Sara Spinelli, Nancy Basile, Daniele Caruso, Giuseppe Falliti, Silvia Dossena, Angela Marino, Rossana Morabito
Summary: This study aimed to verify the protective role of Quercetin in a d-Galactose-induced model of aging in human erythrocytes. It was found that Quercetin preferentially improved lipid peroxidation rather than protein oxidation and prevented glycated hemoglobin formation. These findings suggest that the Band 3 protein could be a potential target for antioxidant treatments against aging-related disturbances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Omar Torres-Quesada, Carolina Doerrier, Sophie Strich, Erich Gnaiger, Eduard Stefan
Summary: This study examines the impact of a newly formulated human plasma-like media (HPLM) on cell growth, mitochondrial bioenergetics, and drug efficacy. It reveals that cells grown in HPLM display altered mitochondrial profiles and that an FDA-approved cancer drug has context-dependent side effects in HPLM. These findings emphasize the importance of selecting a more physiological cell culture medium for analyzing bioenergetic profiles and assessing drug efficacies.
Article
Cell Biology
Alessia Remigante, Sara Spinelli, Elisabetta Straface, Lucrezia Gambardella, Daniele Caruso, Giuseppe Falliti, Silvia Dossena, Angela Marino, Rossana Morabito
Summary: Aging is a decline in physiological functions, closely related to oxidative stress (OS). Functional foods rich in flavonoids are effective in counteracting age-related changes. This study confirmed the protective role of Aca extract in a model of aging in human erythrocytes, reducing OS damage and restoring protein distribution alterations.
Article
Biochemistry & Molecular Biology
Alessia Remigante, Sara Spinelli, Elisabetta Straface, Lucrezia Gambardella, Daniele Caruso, Giuseppe Falliti, Silvia Dossena, Angela Marino, Rossana Morabito
Summary: This study aims to investigate the response of red blood cells to oxidative stress and evaluate the potential beneficial effects of the natural antioxidant quercetin. The results indicate that pre-treatment with quercetin is more effective in protecting red blood cells against oxidative stress and preventing damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Emanuele Bernardinelli, Sebastian Roesch, Edi Simoni, Angela Marino, Gerd Rasp, Laura Astolfi, Antonio Sarikas, Silvia Dossena
Summary: POU3F4 gene mutations are the main cause of X-linked deafness, resulting in hearing loss through impaired transcriptional activity and subcellular distribution. Using RNA sequencing and genetic analysis, researchers found that POU3F4 regulates the transcriptional levels of the amino acid transporter gene SLC6A20, providing insights into the mechanism of POU3F4-related deafness.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Medicine, General & Internal
Arnoldas Matulevicius, Emanuele Bernardinelli, Zippora Brownstein, Sebastian Roesch, Karen B. Avraham, Silvia Dossena
Summary: The SLC26A4 gene mutation is associated with hearing loss and is particularly common in the Ashkenazi Jewish population. Cell-based assays confirmed that the mutant protein has reduced ion transport function, abnormal subcellular localization, and decreased expression levels, supporting its pathogenicity. Mouse experiments further demonstrated the relevance of this protein variant to Pendred syndrome/DFNB4.
JOURNAL OF CLINICAL MEDICINE
(2022)
Editorial Material
Cell Biology
Alessia Remigante, Paola Gavazzo, Rossana Morabito, Silvia Dossena
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alessia Remigante, Sara Spinelli, Angela Marino, Michael Pusch, Rossana Morabito, Silvia Dossena
Summary: Oxidative stress and immune response are important factors in the development of cancers, including melanoma. Ion channels, which are aberrantly expressed in tumor cells, play a role in neoplastic transformation, malignant progression, and resistance to therapy. These ion channels, located in cellular membranes, are targets of oxidative stress, which is particularly elevated in melanoma. They also represent promising targets for therapeutic intervention in melanoma.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Andreas Konopa, Melanie A. Meier, Miriam J. Franz, Emanuele Bernardinelli, Anna-Lena Voegele, Raja Atreya, Silvia Ribback, Stephanie Roessler, Achim Aigner, Kerstin Singer, Stephan Singer, Antonio Sarikas, Susanne Muehlich
Summary: MRTF-A and MRTF-B are coactivators that regulate fundamental biological processes such as cell growth, migration, and differentiation. In hepatocellular carcinoma (HCC), MRTF and SRF activity play a crucial role. This study identifies the G protein-coupled lysophosphatidic acid receptor 1 (LPAR1) as a novel interaction partner of MRTF-A and Filamin A (FLNA), and reveals the potential therapeutic value of inhibiting the LPAR1-FLNA-MRTF-A interaction in HCC therapy.
Review
Biochemistry & Molecular Biology
Emanuele Bernardinelli, Florian Huber, Sebastian Roesch, Silvia Dossena
Summary: X-linked deafness (DFNX) accounts for up to 2% of hereditary hearing loss cases and can occur in syndromic and non-syndromic forms. POU3F4 is the most common gene associated with X-linked deafness and is responsible for about 50% of non-syndromic cases. It plays a crucial role in the development of the middle and inner ear. This article provides an overview of the pathogenic gene variants of POU3F4, discusses the clinical features, and highlights the importance of further research on its transcriptional targets in the ear and brain.
