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.
Article
Multidisciplinary Sciences
Jiayue Su, Desheng Liu, Fan Yang, Mei-Qing Zuo, Chang Li, Meng-Qiu Dong, Shan Sun, Sen-Fang Sui
Summary: The TOM complex, composed of Tom 20, Tom22, and Tom70, plays a crucial role in recognizing and transferring preproteins across the mitochondrial membrane. Cryo-EM structures of the complex have been reported, but the exact function and mechanism of Tom22 and Tom20 as TOM receptors remain unclear. This study provides structural and biochemical insights into their roles in presequence binding and protein translocation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Pharmacology & Pharmacy
Maryne Dupuy, Maxime Gueguinou, Marie Potier-Cartereau, Frederic Lezot, Marion Papin, Aurelie Chantome, Francoise Redini, Christophe Vandier, Franck Verrecchia
Summary: Ion channels play a crucial role in tumor development, with aberrant expression promoting key functions like cell proliferation, resistance to apoptosis, angiogenesis, invasion, and metastasis. Potassium channels are the largest and most diverse family among all ion channels, and this review provides an overview of their role in cancer, including their nomenclature, structure, and their involvement in the control of biological functions that promote tumor development. Additionally, it also focuses on the role of two specific classes of potassium channels, SKCa and Kv1, in cancer progression.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Antoni Wrzosek, Shur Galecka, Monika Zochowska, Anna Olszewska, Bogusz Kulawiak
Summary: Mitochondrial potassium channels play a crucial role in regulating mitochondrial function and cell survival, with potential applications in ischemia/reperfusion injury and cancer treatment.
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
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.
Review
Biochemistry & Molecular Biology
Yevheniia Kravenska, Vanessa Checchetto, Ildiko Szabo
Summary: Potassium ions can enter and exit mitochondria through various channels in the outer and inner membranes, with the ATP-dependent potassium channel being the most studied and playing a crucial role in protecting cells against ischemic and neuronal damage.
Article
Biochemistry & Molecular Biology
Shafqat Rasool, Simon Veyron, Naoto Soya, Mohamed A. Eldeeb, Gergely L. Lukacs, Edward A. Fon, Jean-Francois Trempe
Summary: Mutations in PINK1 lead to Parkinson's disease. The study shows that PINK1 is imported into the translocase of the outer mitochondrial membrane (TOM) complex, leading to its activation by autophosphorylation and initiation of mitochondrial clearance. The crystal structures provide insights into the dimeric autophosphorylation complex and the stabilization mechanism of PINK1 on the core TOM complex.
Article
Medicine, Research & Experimental
Rafal Pawel Kampa, Aleksandra Sek, Adam Szewczyk, Piotr Bednarczyk
Summary: The natural flavonoid quercetin acts as a mitoBKCa channel opener, increasing channel open probability and protecting cells from damage. It enhances cellular migration and depolarizes the mitochondrial membrane, while also increasing gene expression and protein levels of mitoBKCa 133 regulatory subunit. The cytoprotective effects suggest the involvement of BKCa channel activation, providing a new mitochondrial pathway beneficial for vascular endothelial cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Pharmacology & Pharmacy
Chiara Capitani, Ginevra Chioccioli Altadonna, Michele Santillo, Elena Lastraioli
Summary: Despite improvements in treatment, lung cancer continues to be a major global health problem. Adenocarcinoma is the most common subtype, while Small Cell Lung Cancer is the most challenging and difficult to treat. The standard care for these patients involves surgery, radiation therapy, and chemotherapy. The search for novel biomarkers that can aid in diagnosis and therapy is crucial.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biophysics
Ildiko Szabo, Adam Szewczyk
Summary: Mitochondria play a crucial role in various cellular functions, and their proper functioning relies on ion homeostasis. Mitochondrial ion channels control the inner mitochondrial membrane potential, which is essential for mitochondrial function. The discovery of mitochondrial ion channels has provided new insights into the role of ion channels in cell life and death. This review summarizes the biophysical properties, molecular identity, regulation, and therapeutic potential of animal mitochondrial ion channels.
ANNUAL REVIEW OF BIOPHYSICS
(2023)
Article
Multidisciplinary Sciences
Felix Glaser, Petra Hundehege, Etmar Bulk, Luca Matteo Todesca, Sandra Schimmelpfennig, Elke Nass, Thomas Budde, Sven G. Meuth, Albrecht Schwab
Summary: This study investigates whether blocking K(Ca)3.1 channels increases the sensitivity of NSCLC cells towards the EGFR TKI erlotinib and overcomes drug resistance. The results show that K(Ca)3.1 channel blockade can enhance the sensitivity of NSCLC cells to erlotinib, and partial erlotinib resistance can be overcome by this blockade.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Yan Guo, Suxing Jin, Hao Yuan, Tao Yang, Kun Wang, Zijian Guo, Xiaoyong Wang
Summary: Mono-Pt kills cancer cells through a mitophagic pathway by stimulating endoplasmic reticulum stress and activating the unfolded protein response, severely impairing mitochondrial structure and function.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
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)
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
Albert Vallejo-Gracia, Daniel Sastre, Magali Colomer-Molera, Laura Sole, Maria Navarro-Perez, Jesusa Capera, Sara R. Roig, Oriol Pedros-Gamez, Irene Estadella, Orsolya Szilagyi, Gyorgy Panyi, Peter Hajdu, Antonio Felipe
Summary: KCNE4 serves as a crucial regulator in modulating immune system physiology by controlling Kv1.3-associated leukocyte functions.
SCIENTIFIC REPORTS
(2021)
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
Sara R. Roig, Silvia Cassinelli, Maria Navarro-Perez, Mireia Perez-Verdaguer, Irene Estadella, Jesusa Capera, Antonio Felipe
Summary: The Kv beta family is a group of modulators that regulate Kv channels, with Kv beta 2.1 clustering into immunological synapses during leukocyte activation. The localization of Kv beta 2.1 is mainly affected by S-acylation and a pair of C-terminal cysteines, and its targeting to lipid raft microdomains is influenced by various stimuli.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Physiology
Sara R. Roig, Silvia Cassinelli, Andre Zeug, Evgeni Ponimaskin, Antonio Felipe
Summary: Members of the regulatory Kv beta family play a role in modulating the kinetics and traffic of voltage-dependent Kv channels. The formation of heteromeric complexes between Kv beta subtypes influences the spatial distribution in lipid rafts and can alter the immune response. Differentially regulating Kv beta subtypes can modulate Kv beta-dependent physiological responses and the architecture of Kv beta heterotetramers.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Silvia Cassinelli, Carla Vinola-Renart, Anna Benavente-Garcia, Maria Navarro-Perez, Jesusa Capera, Antonio Felipe
Summary: Protein lipidation is a common form of posttranslational modification that regulates various aspects of a protein's physiology, including its structure, stability, and interaction with cellular membranes. Palmitoylation, the addition of long saturated fatty acid chains to proteins, is a key form of lipidation. Enzymes called acyltransferases and thioesterases control the behavior of palmitoylated proteins through a series of acylation and deacylation cycles. Palmitoylation plays a pleiotropic role in regulating the trafficking, spatial organization, and electrophysiological properties of ion channels, particularly voltage-gated ion channels (VGICs). Dysregulation of palmitoylation in VGICs and associated subunits is linked to the development of diseases such as cancer and mental disorders. Therefore, protein palmitoylation is emerging as an important factor in cellular protein regulation and human health.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Dingxi Zhou, Mariana Borsa, Daniel J. Puleston, Susanne Zellner, Jesusa Capera, Sharon Sanderson, Martina Schifferer, Svenja S. Hester, Xin Ge, Roman Fischer, Luke Jostins, Christian Behrends, Ghada Alsaleh, Anna Katharina Simon
Summary: This study identifies interleukin-7 receptor-alpha as a key cargo in proliferating CD4+ T cells within the autophagosomal compartment using a transgenic mouse model. Moreover, the authors uncover the mechanism by which excessive surface interleukin-7 receptor-alpha affects T cell proliferation.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Antonio Felipe, Antonio Ferrer-Montiel
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Maria Navarro-Perez, Irene Estadella, Anna Benavente-Garcia, Ruth Orellana-Fernandez, Anna Petit, Joan Carles Ferreres, Antonio Felipe
Summary: The voltage-gated potassium channel Kv1.3 plays a crucial role in various biological processes, and its altered expression or function is associated with tumorigenesis and cancer progression. Posttranslational modifications, particularly phosphorylation, rapidly modulate channel activity. Additionally, kinases are potential targets in anticancer therapies. This review provides an overview of the kinase-dependent mechanisms and signaling pathways involved in Kv1.3 phosphorylation, highlighting its importance as an anticancer target.