Article
Biology
Jesusa Capera, Mireia Perez-Verdaguer, Roberta Peruzzo, Maria Navarro-Perez, Juan Martinez-Pinna, Armando Alberola-Die, Andres Morales, Luigi Leanza, Ildiko Szabo, Antonio Felipe
Summary: The voltage-gated potassium channel Kv1.3 plays a dual role in immune cells and cancer cells, with its different cellular locations leading to involvement in distinct physiological processes.
Article
Oncology
Jesusa Capera, Mireia Perez-Verdaguer, Maria Navarro-Perez, Antonio Felipe
Summary: Studies have shown that Kv1.3 promotes preadipocyte proliferation by controlling mitochondrial dynamics, playing a significant role in adipogenesis. Kv1.3 is expressed in mitochondria and has an impact on mitochondrial dynamics during the G1/S phase of the cell cycle.
Article
Oncology
Jesusa Capera, Maria Navarro-Perez, Anne Stine Moen, Ildiko Szabo, Antonio Felipe
Summary: Voltage-gated potassium channels, specifically Kv1.3, have important functions in neuronal excitability, cardiac action potentials, and immune response. This study investigates the localization of Kv1.3 in both plasma membrane and mitochondrial membrane, and identifies the TIM23 complex and cytosolic HSP70/HSP90 chaperone complex as crucial factors in the mitochondrial import pathway for Kv1.3. These findings provide insights into the mechanisms and regulation of Kv1.3 localization in mitochondrial membranes.
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Andrea Urbani, Elena Prosdocimi, Andrea Carrer, Vanessa Checchetto, Ildiko Szabo
Summary: Mitochondria are vital organelles involved in cell survival and death. Ion channels in the inner membrane of mitochondria play a crucial role in regulating mitochondrial function and ultimately affecting cell fate. Understanding the regulation of mitochondrial ion channels may lead to the identification of new therapeutic targets for mitochondria-related pathologies.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Bogusz Kulawiak, Piotr Bednarczyk, Adam Szewczyk
Summary: Mitochondria play a vital role in the energy metabolism of cardiac cells, and their dysfunction is implicated in cardiac ischemia/reperfusion injury. Understanding mitochondrial K+ channels can provide insights into the mechanisms of cardioprotection.
Article
Multidisciplinary Sciences
Supriya Ramesha, Sruti Rayaprolu, Christine A. Bowen, Cynthia R. Giver, Sara Bitarafan, Hai M. Nguyen, Tianwen Gao, Michael J. Chen, Ngozi Nwabueze, Eric B. Dammer, Amanda K. Engstrom, Hailian Xiao, Andrea Pennati, Nicholas T. Seyfried, David J. Katz, Jacques Galipeau, Heike Wulff, Edmund K. Waller, Levi B. Wood, Allan Levey, Srikant Rangaraju
Summary: By studying Kv1.3-expressing CNS-MPs in AD mouse models, researchers have identified unique molecular features of these cells and confirmed their microglial origin. Blocking Kv1.3 channels in vivo resulted in reduced Aβ burden, increased anti-inflammatory CNS-MPs, and a prophagocytic phenotype in AD mouse models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Plant Sciences
Feifei Huang, Feihua Wu, Min Yu, Sergey Shabala
Summary: Programmed cell death is a genetically controlled process that eliminates unnecessary or damaged cells. Recent studies have identified nucleotide-binding leucine-rich repeat proteins as a novel class of Ca2+-permeable channels which play a role in plant immune responses. These channels possess a unique structure and can also permeate other cations, making them ideal candidates for mediating cell signaling and adaptive responses to various stress factors, including pathogens and abiotic stresses.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Plant Sciences
Karen C. Chamusco, May N. Milazzo, Kanchan S. Bhan, Terry L. Kamps, Prestina Smith, Modupeoluwa Durojaiye, Cristina D. Moreira, Maria Gallo, Christine D. Chase
Summary: Research found that collapse of CMS-S pollen is a programmed cell death event with morphological features similar to apoptosis regulated by mitochondria in animals. Typically, mitochondrial morphology and activity in CMS-S pollen differ significantly from normal pollen, possibly leading to decreased protection against mitochondrial generation of reactive oxygen species.
Review
Cell Biology
Chang Liu, Zecheng Jiang, Zhongjie Pan, Liang Yang
Summary: Atherosclerosis is a chronic inflammatory vascular disease, and macrophages play a significant role in its progression. Recent studies have highlighted the critical role of programmed cell death in macrophages in the development of vulnerable plaques in atherosclerosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Juan A. Montero, Carlos Ignacio Lorda-Diez, Juan M. Hurle
Summary: This paper proposes a new perspective on the regulation of programmed cell death (PCD) in developing systems based on epigenetics. It challenges the traditional view that PCD is solely controlled by specific gene-encoded signals, arguing that the signals and local tissue interactions responsible for embryonic tissue growth and differentiation play a significant role in PCD. The study suggests that cells retain an epigenetic profile sensitive to DNA damage, resulting in their subsequent elimination.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Zhichao Li, Dandan Li, Renchang Chen, Shang Gao, Zhanwang Xu, Nianhu Li
Summary: Osteoporosis is a metabolic bone disease that occurs due to an imbalance in bone homeostasis. Different types of programmed cell death (PCD) have been found to regulate bone metabolism and natural products derived from dietary components and medicinal plants show potential for the prevention and treatment of osteoporosis. This review discusses the common types of PCD in osteoporosis and the role of natural products in targeting PCDs for the treatment of osteoporosis.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Plant Sciences
Cheng Jiang, Jiawei Wang, Hua-Ni Leng, Xiaqin Wang, Yijing Liu, Haiwen Lu, Meng-Zhu Lu, Jin Zhang
Summary: Developmental programmed cell death (dPCD) plays crucial roles in plant growth and development, especially in industrial production. Despite the identification of key regulators, the complex molecular networks controlling plant dPCD and its original triggers remain elusive.
FRONTIERS IN PLANT SCIENCE
(2021)
Review
Physiology
Bogusz Kulawiak, Adam Szewczyk
Summary: This paper critically reviews the current challenges in mitochondrial potassium channels research. Although there has been substantial progress in understanding K+ traffic in mitochondria, some fundamental issues in this process remain unresolved. The molecular identity of various mitochondrial potassium channels and their interactions with other mitochondrial proteins are discussed in this paper. The posttranslational modifications and pharmacological targeting of mitochondrial potassium channels are also mentioned.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Xin Zhang, Xiulin Lin, Hui Luo, Yuanxing Zhi, Xin Yi, Xiaoyan Wu, Wendi Duan, Ying Cao, Jianxin Pang, Shuwen Liu, Pingzheng Zhou
Summary: Potassium efflux mediated by the Kv1.3 channel plays a critical role in TLR3/4 activation, and pharmacological inhibition of Kv1.3 may be beneficial for treating autoimmune diseases and bacterial infections.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Plant Sciences
Shazia Parveen, Foziya Altaf, Sumira Farooq, Mohammad Lateef Lone, Aehsan ul Haq, Inayatullah Tahir
Summary: Flower senescence is a complex process involving cytological, physiological, and molecular changes, similar to programmed cell death. Ethylene plays a crucial role in ethylene-dependent petal senescence, triggering various changes such as wilting, oxidative stress, protein and nucleic acid degradation, and autophagy. Despite advances in understanding the mechanism and regulation of petal senescence, there are still knowledge gaps that require critical evaluation of the available literature. A deeper understanding of ethylene-dependent senescence can lead to improved regulation of senescence timing and site, resulting in optimized crop yields, enhanced product quality, and extended longevity.
JOURNAL OF EXPERIMENTAL BOTANY
(2023)
Article
Cell Biology
Federica Rossin, Roberto Costa, Matteo Bordi, Manuela D'Eletto, Luca Occhigrossi, Maria Grazia Farrace, Nickolai Barlev, Fabiola Ciccosanti, Silvia Muccioli, Leonardo Chieregato, Ildiko Szabo, Gian Maria Fimia, Mauro Piacentini, Luigi Leanza
Summary: TG2, a multifunctional enzyme, plays essential roles in cellular processes and gene expression, particularly in the Wnt and HSF1 pathways. It has been revealed to regulate HSF1 and Wnt signaling, significantly influencing the overall cellular transcriptome profile. These findings show that TG2 is crucial for the correct embryonal development of lower vertebrates, mediated by the Wnt/HSF1 axis.
CELL DEATH & DISEASE
(2021)
Review
Biochemistry & Molecular Biology
Silvia Muccioli, Valentina Brillo, Leonardo Chieregato, Luigi Leanza, Vanessa Checchetto, Roberto Costa
Summary: The Wnt signaling pathway is crucial in embryonic development for controlling cell proliferation, but aberrant activation in human diseases has been observed. Ion channels, known as modulators of important cellular functions, have been widely researched for their influence on Wnt signaling regulation. This review focuses on the links between ion channels and canonical Wnt signaling, discussing their potential roles in human metabolic diseases, neurological disorders, and cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Roberta Peruzzo, Samantha Corra, Roberto Costa, Michele Brischigliaro, Tatiana Varanita, Lucia Biasutto, Chiara Rampazzo, Daniele Ghezzi, Luigi Leanza, Mario Zoratti, Massimo Zeviani, Cristiano De Pitta, Carlo Viscomi, Rodolfo Costa, Ildiko Szabo
Summary: Pyocyanin, a bacterial redox cycler, has been shown to replace the redox functions of complex III in cells from patients with complex III deficiencies, as well as in genetic models of fruit flies and zebrafish. This suggests the potential use of redox cyclers for the treatment of complex III disorders in mitochondrial diseases.
NATURE COMMUNICATIONS
(2021)
Review
Biology
Valentina Brillo, Leonardo Chieregato, Luigi Leanza, Silvia Muccioli, Roberto Costa
Summary: Mitochondria are key intracellular organelles involved in the metabolic state of the cell and various cellular functions. They release reactive oxygen species (ROS) inside eukaryotic cells, mediating both physiological and pathological cellular functions. Targeting mitochondrial ROS could be a promising strategy to hinder the development of diseases such as cancer.
Article
Biology
Jesusa Capera, Mireia Perez-Verdaguer, Roberta Peruzzo, Maria Navarro-Perez, Juan Martinez-Pinna, Armando Alberola-Die, Andres Morales, Luigi Leanza, Ildiko Szabo, Antonio Felipe
Summary: The voltage-gated potassium channel Kv1.3 plays a dual role in immune cells and cancer cells, with its different cellular locations leading to involvement in distinct physiological processes.
Article
Biochemistry & Molecular Biology
Vitalyi Senyuk, Najmeh Eskandari, Ying Jiang, Rebeca Garcia-Varela, Rachel Sundstrom, Luigi Leanza, Roberta Peruzzo, Mark Burkard, Richard D. Minshall, Saverio Gentile
Summary: Stimulation of the Kv11.1 potassium channel activity in breast cancer cells leads to mitochondrial ROS production and gene expression alterations related to oxidative stress and ER stress. The adaptive response to increased ROS involves Nrf2-dependent transcription of antioxidant genes which promotes cell survival. Inhibition of the Nrf2-mediated antioxidant mechanism sensitizes breast cancer cells to the lethal effects of Kv11.1 activation.
Correction
Biochemistry & Molecular Biology
Roberta Peruzzo, Andrea Mattarei, Michele Azzolini, Katrin Anne Becker-Flegler, Matteo Romio, Giovanni Rigoni, Andrea Carrer, Lucia Biasutto, Sofia Parrasia, Stephanie Kadow, Antonella Manag, Andrea Urbani, Andrea Rossa, Gianpietro Semenzato, Maria Eugenia Soriano, Livio Trentin, Syed Ahmad, Michael Edwards, Erich Gulbins, Cristina Paradisi, Mario Zoratti, Luigi Leanza, Ildiko Szabo
Article
Biochemistry & Molecular Biology
Riccardo Frizzo, Enrico Bortoletto, Tobia Riello, Luigi Leanza, Elisabetta Schievano, Paola Venier, Stefano Mammi
Summary: The hemolymph metabolome of Mytilus galloprovincialis injected with live Vibrio splendidus bacteria showed significant changes in metabolites related to osmoregulation and aerobic respiration. Injection of Vibrio splendidus caused a decrease in amino acids and sugars in mussels acclimated at 18 degrees C, with dynamic metabolic adjustments observed in response to stressful stimuli. NMR-based metabolomics is confirmed as a feasible analytical approach complementary to other omics techniques for studying mussel responses to environmental challenges.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Oncology
Filippo Severin, Andrea Urbani, Tatiana Varanita, Magdalena Bachmann, Michele Azzolini, Veronica Martini, Marco Pizzi, Angelo Paolo Dei Tos, Federica Frezzato, Andrea Mattarei, Paolo Ghia, Maria Teresa Sabrina Bertilaccio, Erich Gulbins, Cristina Paradisi, Mario Zoratti, Gianpietro Carlo Semenzato, Luigi Leanza, Livio Trentin, Ildiko Szabo
Summary: This study reveals that the potassium channels Kv1.3 and IKCa are highly expressed in human chronic lymphocytic leukemia (CLL) cells and inhibiting these channels can kill leukemia cells. The study also shows that PAPTP enhances the therapeutic effect of Venetoclax when used in combination. In a mouse model, PAPTP significantly reduces the number and percentage of CLL cells without toxicity. In contrast, TRAM-34 does not show any beneficial effects in the mouse experiment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Vanessa Checchetto, Luigi Leanza, Diego De Stefani, Rosario Rizzuto, Erich Gulbins, Ildiko Szabo
Summary: The field of mitochondrial ion channels has rapidly developed in the past decade due to molecular identification and specific pharmacological targeting. Despite challenges in genetic manipulation of mitochondrial K+ channels, they are recognized to play important roles in various pathologies and are druggable targets for potential therapeutic interventions. The in-depth investigation of mitochondrial potassium channels may lead to the development of innovative small molecules with significant therapeutic potential.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Cell Biology
Silvia Muccioli, Roberto Ciaccio, Valentina Brillo, Luigi Leanza
Summary: Tissue Transglutaminases (TGs) are crosslinking enzymes that play a role in the development and progression of cancers by remodeling the tumor microenvironment. This study investigated the distribution and prognostic significance of TGs in cancer patients using publicly available datasets. The results showed that skin cutaneous melanoma (SKCM) had the highest abundance of TGs mutations. Among all TGs, TG2 was the only member whose expression was associated with better overall survival in SKCM, despite its increased expression with worsening tumor phenotype. The analysis revealed a positive association between TG2 expression and anti-tumoral immune response, suggesting TG2 as a promising immune biomarker for prognosis in SKCM.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Beatrice Angi, Silvia Muccioli, Ildiko Szabo, Luigi Leanza
Summary: Potassium channels are highly expressed in cancer cells and play a role in cell proliferation by modulating various cellular processes. This study investigated the correlation between Kv channel expression and survival rate in five different types of cancer. The analysis revealed a prognostic role of specific Kv channel genes in certain cancer types, and differences in gene expression and immune cell infiltration may contribute to the observed differences in prognosis. Overall, the study highlights the promising correlation between Kv channel expression and survival rate in cancer.
Article
Cell Biology
Doni Davide, Cavion Federica, Bortolus Marco, Baschiera Elisa, Muccioli Silvia, Tombesi Giulia, d'Ettorre Federica, Daniele Ottaviani, Marchesan Elena, Leanza Luigi, Greggio Elisa, Ziviani Elena, Russo Antonella, Bellin Milena, Sartori Geppo, Carbonera Donatella, Salviati Leonardo, Costantini Paola
Summary: Friedreich ataxia (FRDA) is a rare neurodegenerative disease caused by an expanded GAA repeat in the FXN gene, leading to reduced expression of frataxin. This study explores the interaction between frataxin and respiratory complexes I, II and III, and finds that the decreased level of frataxin specifically affects the FeS cluster content of complex I in FRDA patients' cells. Additionally, a frataxin-like protein from a different organism is found to improve the mitochondrial respiratory phenotype in FRDA patients' cells.
CELL DEATH & DISEASE
(2023)
Meeting Abstract
Psychiatry
C. Idotta, E. Tibaldi, N. Favaretto, M. Pagano, R. Peruzzo, G. Pigato, D. Cazzador, P. Meneguzzo, M. Solmi, L. Leanza, A. Favaro, A. M. Brunati, T. Toffanin
EUROPEAN PSYCHIATRY
(2021)
Meeting Abstract
Biophysics
M. Bachmann, A. Rossa, G. Antoniazzi, L. Biasutto, A. Carrer, M. Campagnaro, L. Leanza, M. Gonczi, L. Csernoch, C. Paradisi, A. Mattarei, M. Zoratti, I. Szabo
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Brandon P. Russell, David J. Vinyard
Summary: The Mn4CaO5 oxygen-evolving complex in Photosystem II is crucial for water oxidation. D1 residue R334 participates in proton release and interacts with PsbO. A D1-R334G mutant destabilizes the OEC but stabilizes the S2 intermediate.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2024)
Article
Biochemistry & Molecular Biology
Alexander A. Bulychev, Tatiana S. Strelets
Summary: Excitable cells of higher plants and characean algae respond to stressful stimuli by generating action potentials that influence chlorophyll fluorescence and photosynthesis for an extended period of time. While plant leaves exhibit a reversible depression in the efficiency of photosystem II reaction after an individual action potential, characean algae show long-lasting oscillations of photosystem II reaction efficiency after firing an action potential. This study investigates the possible mechanisms behind these oscillations and suggests that they are a result of metabolic rearrangements in chloroplasts and the cyclosis cessation-recovery cycle induced by calcium influx during action potentials. The findings also indicate that fluidic communications between different cell regions play a role in these oscillations, and the inhibition of oscillations occurs when these communications are restricted or eliminated.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2024)
Article
Biochemistry & Molecular Biology
Dmitry Zlenko, Elena A. Protasova, Georgy Tsoraev, Nikolai N. Sluchanko, Dmitry A. Cherepanov, Thomas Friedrich, Baosheng Ge, Song Qin, Eugene G. Maksimov, Andrew B. Rubin
Summary: The conformation of chromophores in isolated phycobiliproteins is heterogeneous, but not in the entire phycobilisome (PBS). Under low-energy excitation, there is no significant uphill energy transfer from the core to the peripheral rods of the PBS, while transfer from the terminal emitters to bulk allophycocyanin chromophores is highly probable.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2024)
Article
Biochemistry & Molecular Biology
Makio Yokono, Chiyo Noda, Jun Minagawa
Summary: This paper investigates the energy transfer between Photosystem II and Photosystem I in Arabidopsis thaliana, and finds that the fast spillover is reversibly regulated depending on pH.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2024)
