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
Multidisciplinary Sciences
Elisa B. Randi, Karim Zuhra, Laszlo Pecze, Theodora Panagaki, Csaba Szabo
Summary: In mammalian cells, cyanide exhibits a biphasic effect on mitochondrial Complex IV activity, stimulating it at low concentrations and inhibiting it at higher concentrations. Low levels of cyanide lead to increased cell proliferation and ATP production, while higher levels result in inhibition of cellular bioenergetics. The presence of cyanide-producing enzymes in mammalian cells suggests a regulatory role for endogenous cyanide.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Nonhlakanipho F. Sangweni, Phiwayinkosi V. Dludla, Nireshni Chellan, Lawrence Mabasa, Jyoti R. Sharma, Rabia Johnson
Summary: The study found that DMSO concentrations lower than 0.5% can enhance respiratory control ratio and cellular viability in cardiomyoblasts, while exposure to 3.7% DMSO increases apoptosis in cardiomyoblasts due to mitochondrial dysfunction and oxidative stress. In cancer cells, DMSO at concentrations equal to or higher than 0.009 reduces maximal respiratory capacity and ATP-linked respiration, leading to increased ROS production and apoptosis. Surprisingly, 0.001% DMSO exposure resulted in increased proliferative activity in cancer cells. These findings suggest caution when using DMSO in cancer cells, while demonstrating no cytotoxic effects or therapeutic benefits at concentrations equal to or lower than 0.5% in cardiomyoblasts.
Review
Cell Biology
Ruoxi Zhang, Rui Kang, Daniel J. Klionsky, Daolin Tang
Summary: Ion exchange between intracellular and extracellular spaces is crucial for cell metabolism and signal transduction. Autophagy, as a lysosomal-dependent degradation pathway, regulates cellular homeostasis through recycling of components and is influenced by ion channels and transporters. ATG proteins are central to the formation of autophagy-related structures, while the regulation of autophagy in mammalian cells involves ion channels and transporters.
Review
Cardiac & Cardiovascular Systems
Mary Audrey D. Viloria, Qing Li, Wang Lu, Nguyen Thanh Nhu, Yijie Liu, Zhen-Yang Cui, Yu-Jung Cheng, Shin-Da Lee
Summary: Exercise training has positive effects on cardiac mitochondrial respiration and quality control in patients with ischemic heart disease, including decreased reactive oxygen species production, increased mitochondrial activity, and improved biogenesis, dynamics, and mitophagy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Endocrinology & Metabolism
Antoine Stier
Summary: Research has shown the presence of cell-free mitochondria in human blood, but they are unlikely to be functional in vivo. They may retain a nonfunctional part of the mitochondrial electron transport system.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Multidisciplinary Sciences
Kirin D. Gada, Mengmeng Chang, Aishwarya Chandrashekar, Leigh D. Plant, Sami F. Noujaim, Diomedes E. Logothetis
Summary: G-protein-gated inwardly rectifying potassium (GIRK) channel activity is regulated by phosphatidylinositol-4,5-bisphosphate (PI 4,5P(2)), and PKC epsilon plays a role in the activation of GIRK channels in cardiac atrial cells and human stem cell-derived atrial cardiomyocytes. PKC epsilon enhances the interaction between GIRK4 and GIRK1/4 with PIP2, leading to increased channel activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Camille E. Blandin, Basile J. Gravez, Stephane N. Hatem, Elise Balse
Summary: Both inherited and acquired cardiac arrhythmias are often linked to abnormal functional expression of ion channels at the cellular level, with mutations in genes encoding ion channels being a major factor in inherited cases. Disruption of normal channel trafficking due to factors like fibrosis and altered myocyte contacts is common in acquired cardiac arrhythmias. Channel availability, particularly in hERG and K(V)1.5 channels, may be another significant arrhythmogenic mechanism. Knowledge of these molecular mechanisms could lead to novel antiarrhythmic strategies.
Article
Biochemistry & Molecular Biology
Carmen Mannella
Summary: VDAC is the main metabolite pore in the mitochondrial outer membrane with open and partially closed states. By predicting structures, we found that modified VDAC sequences can exhibit different conformational states, providing clues for understanding alternative structures of VDAC.
Article
Endocrinology & Metabolism
Mehmet M. Altintas, Salvatore DiBartolo, Lana Tadros, Beata Samelko, Haimanot Wasse
Summary: This study aimed to elucidate mitochondrial function and associated stress pathologies in kidney disease using peripheral blood mononuclear cells (PBMCs) of hemodialysis patients. The analysis revealed a significant reduction in mitochondrial respiration in ESKD patient PBMCs, correlated with changes in key bioenergetic parameters and protein expression levels. The findings suggest a link between mitochondrial dysfunction and ESKD, with potential therapeutic implications.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biology
Stefano Bettinazzi, Liliana Milani, Pierre U. Blier, Sophie Breton
Summary: The study explores the impact of sex-specific mitochondrial evolution on gamete bioenergetics in DUI and SMI bivalve species. The findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes, resulting in decreased enzymatic capacity in DUI sperm, especially at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. The origin of this phenotype, whether from positive or relaxed selection acting on DUI sperm, remains uncertain.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ildiko Szabo, Mario Zoratti, Lucia Biasutto
Summary: Targeting mitochondrial ion channels with drugs to eliminate cancer cells is a promising approach due to differential expression and/or regulation of these channels in cancer cells compared to healthy cells. Modulation of ion channels can indirectly affect oxidative phosphorylation, which may be crucial for cancer and cancer stem cell survival. Additionally, modulation of mitochondrial ion channels leading to cytochrome c release may be advantageous in overcoming drug resistance.
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
Sport Sciences
Erik D. Marchant, Nathan D. Marchant, Robert D. Hyldahl, Jayson R. Gifford, Michael W. Smith, Chad R. Hancock
Summary: This study aimed to investigate the effects of ultraendurance exercise on the bioenergetic status of muscle. The findings showed that completing a 100 km ultramarathon led to significant mitochondrial impairment in muscle, which rapidly recovered within two days. Blood markers also showed changes after the run but partially recovered within 48 hours.
MEDICINE & SCIENCE IN SPORTS & EXERCISE
(2021)
Review
Plant Sciences
Dev T. Britto, Devrim Coskun, Herbert J. Kronzucker
Summary: This paper focuses on the biological potassium acquisition and utilization processes in modern vascular plants over an evolutionary timescale, and delves into several prominent themes in plant K+ -transport physiology.
JOURNAL OF PLANT PHYSIOLOGY
(2021)
Article
Cell Biology
Julie A. Dougherty, Nil Patel, Naresh Kumar, Shubha Gururaja Rao, Mark G. Angelos, Harpreet Singh, Chuanxi Cai, Mahmood Khan
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Ji Young Kim, Yuntao Bai, Laura A. Jayne, Ralph D. Hector, Avinash K. Persaud, Su Sien Ong, Shreshtha Rojesh, Radhika Raj, Mei Ji He Ho Feng, Sangwoon Chung, Rachel E. Cianciolo, John W. Christman, Moray J. Campbell, David S. Gardner, Sharyn D. Baker, Alex Sparreboom, Rajgopal Govindarajan, Harpreet Singh, Taosheng Chen, Ming Poi, Katalin Susztak, Stuart R. Cobb, Navjot Singh Pabla
NATURE COMMUNICATIONS
(2020)
Review
Physiology
Devasena Ponnalagu, Harpreet Singh
FRONTIERS IN PHYSIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Nathalie Tombo, Abdulhafiz D. Imam Aliagan, Yansheng Feng, Harpreet Singh, Jean C. Bopassa
FREE RADICAL BIOLOGY AND MEDICINE
(2020)
Article
Obstetrics & Gynecology
Mitali Sahni, Bettie Yeboah, Pragnya Das, Dilip Shah, Devasena Ponnalagu, Harpreet Singh, Leif D. Nelin, Vineet Bhandari
JOURNAL OF PERINATOLOGY
(2020)
Article
Virology
Katherine E. Nolan, Lisa A. Baer, Priyanka Karekar, Andrew M. Nelson, Kristin I. Stanford, Lauren M. Doolittle, Lucia E. Rosas, Judy M. Hickman-Davis, Harpreet Singh, Ian C. Davis
Summary: This study found that inhibiting glycolysis worsens outcomes of influenza infection, while promoting TCA cycle flux and inhibiting OXPHOS can mitigate the effects of the virus. These findings suggest that a shift to glycolysis may be host-protective in influenza.
Article
Biochemistry & Molecular Biology
Priyanka Karekar, Haley N. Jensen, Kathryn L. G. Russart, Devasena Ponnalagu, Sarah Seeley, Shridhar Sanghvi, Sakima A. Smith, Leah M. Pyter, Harpreet Singh, Shubha Gururaja Rao
Summary: The study suggests that tumor induction may cause cardiac dysfunction even before treatment or onset of cachexia. By investigating the Hippo-Yorkie pathway, it is found that Yki overexpression compromises cardiac function, which can be rescued with antioxidant treatment.
Article
Cell Biology
Shridhar Sanghvi, Kalina Szteyn, Devasena Ponnalagu, Divya Sridharan, Alexender Lam, Inderjot Hansra, Ankur Chaudhury, Uddalak Majumdar, Andrew R. Kohut, Shubha Gururaja Rao, Mahmood Khan, Vidu Garg, Harpreet Singh
Summary: This study reveals the presence of BKCa channels in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, and demonstrates their protective effect on the heart. Inhibition of plasma membrane BKCa channels can protect the neonatal heart from ischemia-reperfusion injury.
CELL DEATH DISCOVERY
(2022)
Article
Nutrition & Dietetics
May M. Cheung, Rosemary D. Dall, Patricia A. Shewokis, Asma Altasan, Stella L. Volpe, Renee Amori, Harpreet Singh, Deeptha Sukumar
Summary: This study found that combined magnesium and vitamin D treatment may be more effective in increasing serum 25OHD concentrations compared to vitamin D supplementation alone in overweight and obese individuals, and it also has the potential to lower baseline systolic blood pressure.
Article
Multidisciplinary Sciences
Devasena Ponnalagu, Shanna Hamilton, Shridhar Sanghvi, Diego Antelo, Neill Schwieterman, Inderjot Hansra, Xianyao Xu, Erhe Gao, John C. Edwards, Shyam S. Bansal, Loren E. Wold, Dmitry Terentyev, Paul M. L. Janssen, Thomas J. Hund, Mahmood Khan, Andrew R. Kohut, Walter J. Koch, Harpreet Singh
Summary: Mitochondrial-associated membranes (MAMs) play a crucial role in modulating cellular response to myocardial ischemia-reperfusion (IR) injury. The chloride intracellular channel protein (CLIC4), found in MAMs of cardiomyocytes, is involved in regulating ER and mitochondrial calcium homeostasis. Loss of CLIC4 increases myocardial infarction and impairs cardiac function after IR injury. CLIC4 deficiency leads to increased apoptosis and mitochondrial dysfunction in cardiomyocytes.
Article
Nanoscience & Nanotechnology
Syed Baseeruddin Alvi, Divya Sridharan, Shridhar K. Sanghvi, Muhamad Mergaye, Uzair Ahmed, Sarah K. Mikula, Harpreet Singh, Mahmood Khan
Summary: This study demonstrates the potential of polydopamine nanoparticles (PDA-NPs) as a bioactive agent to enhance contractility and beat propagation of cardiomyocytes. PDA-NPs improve mitochondrial bioenergetics and have cardiotonic effects on the heart. In addition, they can modulate the genetic expression of cardiomyocytes.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Nutrition & Dietetics
Rosemary D. Dall, May M. Cheung, Patricia A. Shewokis, Asma Altasan, Stella L. Volpe, Renee Amori, Harpreet Singh, Deeptha Sukumar
Summary: High-dose vitamin D supplementation may reduce insulin resistance by increasing total osteocalcin concentrations in individuals at risk for prediabetes or diabetes mellitus. This study aimed to investigate the combined effect of vitamin D and magnesium supplementation on glycemic indices and bone turnover markers in overweight and obese individuals. The results showed that combined supplementation did not lead to short-term improvements in glycemic indices or bone turnover markers.
NUTRITION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Veronica Loyo-Celis, Devendra Patel, Shridhar Sanghvi, Kamalpreet Kaur, Devasena Ponnalagu, Yang Zheng, Sahej Bindra, Harmeet Rireika Bhachu, Isabelle Deschenes, Shubha Gururaja Rao, Harpreet Singh
Summary: CLIC6 is a protein implicated in various cancers and known to interact with dopamine receptors. This study characterized the biophysical properties of CLIC6 and found it to localize to the plasma membrane, exhibit high permeability to chloride ions, and be regulated by pH and redox potential.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Endocrinology & Metabolism
Rizaldy C. Zapata, Dinghong Zhang, Dongmin Yoon, Chanond A. Nasamran, Daisy R. Chilin-Fuentes, Avraham Libster, Besma S. Chaudry, Mariela Lopez-Valencia, Devasena Ponnalagu, Harpreet Singh, Michael Petrascheck, Olivia Osborn
Summary: Clic1 inhibition reduces food intake and body weight in mouse models, suggesting it as a potential therapeutic target for obesity treatment.
MOLECULAR METABOLISM
(2023)