Review
Biochemistry & Molecular Biology
Melissa J. S. MacEwen, Yasemin Sancak
Summary: Mitochondrial calcium signaling plays a crucial role in regulating various cellular functions, including energy production, cytoplasmic signaling, and cell death. The mitochondrial calcium uniporter complex (MCUC) is essential for calcium flux into the mitochondria. Recent studies have revealed the structure, regulation, and new functions of MCUC, highlighting its potential therapeutic importance for human health.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Review
Biochemistry & Molecular Biology
Giorgia Pallafacchina, Sofia Zanin, Rosario Rizzuto
Summary: Advances in scientific research have led to increasing interest in the regulation and physiological role of mitochondrial Ca2+ signaling, with the discovery and characterization of genes and pathways involved in recent years. The identification of the mitochondrial channel components and their function over the past decade has provided a clearer understanding of the role of mitochondrial Ca2+ signals in cellular processes. Recent studies have highlighted the importance of the MCU complex in controlling muscle nutrition and metabolism.
Article
Biology
Vivek Garg, Junji Suzuki, Ishan Paranjpe, Tiffany Unsulangi, Liron Boyman, Lorin S. Milescu, W. Jonathan Lederer, Yuriy Kirichok
Summary: The study reveals that the MICU subunits do not block the MCUcx pore in the absence or presence of extramitochondrial Ca2+, but instead potentiate MCUcx activity by modifying its gating properties to spend more time in the open state when extramitochondrial Ca2+ is elevated.
Article
Multidisciplinary Sciences
Akshar Patel, Matthew Simkulet, Soumya Maity, Manigandan Venkatesan, Anastasios Matzavinos, Muniswamy Madesh, B. Rita Alevriadou
Summary: This study found that under shear stress, the increase in mitochondrial Ca2+ levels is associated with the function and energy metabolism of endothelial cells. Activation of the mechanosensitive channel Piezo1 and the endothelial nitric oxide synthase eNOS are involved in this process.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Yuan Gao, Xiaoyu Zhang, Ximeng Li, Ruijuan Qi, Yixin Han, Yuan Kang, Runlan Cai, Cheng Peng, Yun Qi
Summary: Aloe-emodin, a naturally occurring anthraquinone, was identified as a potent mast cell stabilizer that can significantly inhibit mast cell degranulation by enhancing mitochondrial Ca2+ uptake and decreasing cytosolic Ca2+ concentration. This study provides a promising candidate for the treatment of mast cell activation-related diseases.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Cell Biology
Alicia G. Gomez-Valades, Macarena Pozo, Luis Varela, Mehdi Boutagouga Boudjadja, Sara Ramirez, Inigo Chivite, Elena Eyre, Roberta Haddad-Tovolli, Arnaud Obri, Maria Mila-Guasch, Jordi Altirriba, Marc Schneeberger, Monica Imbernon, Angela R. Garcia-Rendueles, Pau Gama-Perez, Jonathan Rojo-Ruiz, Bence Racz, Maria Teresa Alonso, Ramon Gomis, Antonio Zorzano, Giuseppe D'Agostino, Clara Alvarez, Ruben Nogueiras, Pablo M. Garcia-Roves, Tamas L. Horvath, Marc Claret
Summary: This study demonstrates that the expression of the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons is influenced by fluctuations in nutrient availability, and genetic inactivation of OPA1 in these neurons leads to alterations in mitochondrial topology, Ca2+ handling, and metabolic hormone a-MSH expression, ultimately resulting in obesity. Pharmacological blockade of mitochondrial Ca2+ influx can restore a-MSH levels and improve metabolic defects in mutant mice, indicating a potential therapeutic approach for obesity.
Article
Biochemistry & Molecular Biology
Michael P. Young, Zachary T. Schug, David M. Booth, David Yule, Katsuhiko Mikoshiba, Gyorgy Hajnoczky, Suresh K. Joseph
Summary: The interplay between calcium signaling and cellular metabolism is not well understood. In this study, the authors investigated the metabolic and bioenergetic responses of human cancer cells with loss of cytosolic and/or mitochondrial calcium signaling. The results showed that constitutive calcium signaling is dispensable for the bioenergetic needs of the cells, but increased energy expenditure in mitochondria-deficient cells may lead to bioenergetic failure under metabolic stress.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Hao Wu, Benjamin Brand, Miriam Eckstein, Sophia M. Hochrein, Magdalena Shumanska, Jan Dudek, Alexander Nickel, Christoph Maack, Ivan Bogeski, Martin Vaeth
Summary: The study demonstrates that mitochondrial Ca2+ uptake is largely dispensable for murine T cell function, despite an increase in cytosolic Ca2+ levels with genetic inactivation of MCU. The discrepancy between this study and previous reports suggests compensatory mechanisms in MCU-deficient mice and/or off-target effects of current MCU inhibitors.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Multidisciplinary Sciences
Wenping Wu, Jimin Zheng, Zongchao Jia
Summary: The mitochondrial uniporter is a Ca2+-selective ion-conducting channel in the inner mitochondrial membrane composed of MCU, MCUb, EMRE, MICU1, and MICU2. Recent structural studies have provided insights into the component structures and their spatial relationship, contributing to a better understanding of mitochondrial Ca2+ uptake and regulation. Further research in this area could lead to advancements in studying mitochondrial Ca2+ permeation and related diseases.
Article
Biochemistry & Molecular Biology
Macarena Rodriguez-Prados, Kai-Ting Huang, Katalin Marta, Melanie Paillard, Gyorgy Csordas, Suresh K. Joseph, Gyorgy Hajnoczky
Summary: Mitochondrial Ca2+ homeostasis is dysregulated in many diseases and can be targeted therapeutically. The uniporter channel (mtCU), comprised of MCU and regulated by MICU1, plays a crucial role in mitochondrial Ca2+ uptake. Understanding the molecular mechanisms of mtCU activators and inhibitors is essential for developing effective therapies.
CELL CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Veronica Costiniti, Guilherme H. S. Bomfim, Maria Neginskaya, Ga-Yeon Son, Erna Mitaishvili, Marta Giacomello, Evgeny Pavlov, Rodrigo S. Lacruz
Summary: This study analyzed the functional features of mitochondria in rat ameloblasts and found an increased mitochondrial Ca2+ handling in the maturation stage, particularly in response to Ca2+ influx via store-operated Ca2+ entry (SOCE). These findings provide insights into the role of mitochondria in enamel and suggest that SOCE and mitochondrial Ca2+ uptake are complementary processes in biological mineralization.
Article
Biochemistry & Molecular Biology
Dhanendra Tomar, Manfred Thomas, Joanne F. Garbincius, Devin W. Kolmetzky, Oniel Salik, Pooja Jadiya, Suresh K. Joseph, April C. Carpenter, Gyorgy Hajnoczky, John W. Elrod
Summary: MICU1 is a Ca2+-binding protein that regulates mitochondrial Ca2+ uptake and membrane dynamics independently of matrix Ca2+ content. MICU1 interacts with MICOS components MIC60 and CHCHD2 to form the MICOS complex and is essential for proper mitochondrial architecture and cell death signaling. This system allows distinct Ca2+ signaling in the mitochondrial matrix and intermembrane space to modulate cellular energetics and cell death in a coordinated manner.
Article
Biochemistry & Molecular Biology
Rongjin Yang, Xiaomeng Zhang, Pingping Xing, Shun Zhang, Feiyu Zhang, Jianbang Wang, Jun Yu, Xiaoling Zhu, Pan Chang
Summary: This study demonstrated that Grpel2 expression is upregulated during myocardial ischemia/reperfusion (I/R) injury. Knockdown of Grpel2 exacerbates mitochondrial fission, cardiomyocyte death, and cardiac contractile dysfunction induced by I/R injury. The study also showed that Grpel2 knockdown increases the expression of MCU and mitochondrial calcium content.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Jiho Yoo
Summary: Mitochondria, organelles responsible for various cellular functions, uptake Ca2+ ions through the MCU holo-complex. The protein structure of the MCU holo-complex has recently been identified, providing insights into the uptake and regulation mechanisms.
Article
Biology
Li Zhang, Felicia Dietsche, Bruno Seitaj, Liliana Rojas-Charry, Nadina Latchman, Dhanendra Tomar, Rob C. Wust, Alexander Nickel, Katrin B. M. Frauenknecht, Benedikt Schoser, Sven Schumann, Michael J. Schmeisser, Johannes vom Berg, Thorsten Buch, Stefanie Finger, Philip Wenzel, Christoph Maack, John W. Elrod, Jan B. Parys, Geert Bultynck, Axel Methner
Summary: Ion fluxes across the inner mitochondrial membrane play crucial roles in controlling mitochondrial volume, energy production, and apoptosis. TMBIM5, a highly conserved protein, is involved in maintaining mitochondrial cristae architecture, ATP production, and apoptosis. Overexpression of TMBIM5 can mediate mitochondrial calcium uptake, while loss of TMBIM5 results in increased potassium and reduced proton levels in the mitochondrial matrix.
LIFE SCIENCE ALLIANCE
(2022)
Article
Cell Biology
Benjamin Gottschalk, Corina T. Madreiter-Sokolowski, Wolfgang F. Graier
Summary: This article focuses on the synergistic control of OPA1 and MICU1 on the cristae junction, highlighting the critical role of the adaptive cristae junction permeability in regulating various mitochondrial functions. Specifically, it discusses the impact of MICU1-regulated cristae junction on the activity and distribution of MCU within the complex ultrastructure of mitochondria.
Article
Biology
Zhanat Koshenov, Furkan E. Oflaz, Martin Hirtl, Benjamin Gottschalk, Rene Rost, Roland Malli, Wolfgang F. Graier
Summary: The study investigates the regulation of basal mitochondrial bioenergetics and reveals that Ca2+ fluxes from ER-mitochondria contact sites control basal mitochondrial metabolism and energetics. The researchers identify citrin as a primary regulator of this process and show that manipulation of Ca2+ dynamics can reprogram cellular and mitochondrial metabolism.
COMMUNICATIONS BIOLOGY
(2022)
Article
Transplantation
Andras T. Deak, Katarina Belic, Anna-Maria Meissl, Katharina Artinger, Kathrin Eller, Bernd Rechberger, Tobias Niedrist, Wolfgang F. Graier, Roland Malli, Helmut Bischof, Sandra Burgstaller, Sandra Blass, Alexander Avian, Alexander R. Rosenkranz, Alexander H. Kirsch
Summary: This study assessed the performance of genetically encoded potassium-ion indicators (GEPIIs) in measuring salivary potassium concentration and found that salivary potassium levels exhibited similar kinetics to plasma potassium levels. However, further research is needed to determine if saliva could be a suitable sample type for monitoring plasma potassium levels.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Chemistry, Medicinal
Veerawat Teeranachaideekul, Warisara Parichatikanond, Varaporn Buraphacheep Junyaprasert, Boontida Morakul
Summary: PSO-loaded niosomes show better skin permeation and hair follicle accumulation, inhibiting 5 alpha-reductase activity and hindering IL-6 activity. The hair scalp serum with PSO-loaded niosomes does not cause irritation to human skin and significantly reduces hair loss and increases the anagen to telogen (A/T) ratio.
Article
Cell Biology
Furkan E. Oflaz, Zhanat Koshenov, Martin Hirtl, Olaf A. Bachkoenig, Wolfgang F. Graier, Benjamin Gottschalk
Summary: Mitochondrial uncoupling proteins UCP1 and UCP2 have different molecular mechanisms for executing their mitochondria uncoupling function, with UCP1 dissipating the proton motive force and UCP2 modulating the permeability of the cristae junction. This mini-review discusses the molecular mechanisms of UCP1 in brown adipose tissue and UCP2 in aged and cancer non-excitable cells, and the synergistic effects of both UCPs with the mitochondrial Ca2+ uptake machinery.
Article
Genetics & Heredity
Lukas Kaufmann, Johannes Pilic, Lisa Auinger, Anna-Lena Mayer, Jasmin Blatterer, Johann Semmler-Bruckner, Safdar Abbas, Khurram Rehman, Muhammad Ayaz, Wolfgang F. Graier, Roland Malli, Erwin Petek, Klaus Wagner, Ali Al Kaissi, Muzammil Ahmad Khan, Christian Windpassinger
Summary: Restrictive dermopathy (RD) is a lethal condition caused by loss-of-function mutations in ZMPSTE24, while mutations preserving residual enzymatic activity lead to mandibuloacral dysplasia with type B lipodystrophy (MADB) phenotype. A new homozygous loss-of-function mutation in ZMPSTE24 was identified in two consanguineous Pakistani families with MADB. Functional analysis revealed that alternative translation initiation sites were utilized, preventing complete loss of protein function and explaining the relatively mild phenotype in affected patients. Our findings suggest considering the creation of new potential start codons in other disease-associated genes with N-terminal mutations.
Article
Biochemistry & Molecular Biology
Madeleine Goeritzer, Katharina B. Kuentzel, Sarah Beck, Melanie Korbelius, Silvia Rainer, Ivan Bradic, Dagmar Kolb, Marion Mussbacher, Waltraud C. Schrottmaier, Alice Assinger, Axel Schlagenhauf, Rene Rost, Benjamin Gottschalk, Thomas O. Eichmann, Thomas Zuellig, Wolfgang F. Graier, Nemanja Vujic, Dagmar Kratky
Summary: Monoglyceride lipase (MGL) hydrolyzes monoacylglycerols (MG) and plays a role in platelet function. MGL deficiency leads to decreased platelet aggregation and impaired response to collagen activation, resulting in reduced thrombus formation and prolonged bleeding time. Genetic deletion of MGL is associated with altered thrombogenesis in mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Mathematics, Interdisciplinary Applications
Claire Jean-Quartier, Katharina Bein, Lukas Hejny, Edith Hofer, Andreas Holzinger, Fleur Jeanquartier
Summary: In response to socioeconomic development, this study focuses on the transparency and sustainability aspects of artificial intelligence in terms of energy consumption. The research measures carbon emissions and energy consumption of Python algorithms and tests the impact of explainability on algorithmic energy consumption. The results can guide the selection of tools to measure algorithmic energy consumption and raise awareness of emission-based model optimization by highlighting the sustainability of explainable artificial intelligence.
Article
Gastroenterology & Hepatology
Sarah Duponchel, Lea Monnier, Jennifer Molle, Nadia Bendridi, Muhammad Rizwan Alam, Ahmed Gaballah, Boyan Grigorov, Alexander Ivanov, Marcel Schmiel, Margarete Odenthal, Michel Ovize, Jennifer Rieusset, Fabien Zoulim, Birke Bartosch
Summary: Chronic HCV infection causes cellular stress, fibrosis, and predisposes to hepatocarcinogenesis. Mitochondria play key roles in orchestrating stress responses. The study revealed that HCV proteins associate with mitochondria and alter the composition of mitochondrial subdomains, which are crucial for efficient viral replication.
Editorial Material
Cell Biology
Benjamin Gottschalk, Roland Malli, Wolfgang F. Graier
Summary: Changes in mitochondrial ultrastructure and dynamics, including cytochrome c release, membrane potential rearrangement, and mitochondrial Ca2+ uptake dynamics, are observed in MICU1(-/-) cells due to its sensitivity to Ca2+ and its binding to Mic60 and CHCHD2. MICU1 is not only an interaction partner and regulator of the MCU complex, but also plays a crucial role in determining mitochondrial ultrastructure and initiating apoptosis.
Article
Biochemistry & Molecular Biology
Madiha Amin Malik, Muhammad Arif Nadeem Saqib, Edwin Mientjes, Anushree Acharya, Muhammad Rizwan Alam, Ilse Wallaard, Isabelle Schrauwen, Michael J. Bamshad, Regie Lyn P. Santos-Cortez, Ype Elgersma, Suzanne M. Leal, Muhammad Ansar
Summary: Intellectual disability (ID) and retinal dystrophy (RD) are common features of multiple syndromes. A study on a family with severe ID and retinitis pigmentosa (RP) identified a genetic variant in the AGPAT3 gene, suggesting its role in the development of ID and RP syndrome.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Chemistry, Multidisciplinary
Zuzana Klepcova, Ivana Spakova, Corina T. T. Madreiter-Sokolowski, Wolfgang Graier, Katarina Kalinova, Erika Samolova, Romana Smolkova, Lukas Smolko, Miroslava Rabajdova
Summary: Two novel Mn(II) complexes with fenamic acid and flufenamic acid as ligands and neocuproine as a supporting ligand were synthesized and characterized. The complexes exhibit moderate radical scavenging activity and cytotoxic effects on selected cell lines, with the flufenamic acid complex being able to induce apoptosis. Both complexes target inflammatory processes on a cellular level.
NEW JOURNAL OF CHEMISTRY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
I. Spakova, Z. Klepcova, L. Smolko, M. Marekova, W. F. Graier, M. Rabajdova
Meeting Abstract
Biochemistry & Molecular Biology
Z. Klepcova, I. Spakova, L. Smolko, M. Marekova, W. F. Graier, M. Rabajdova
Article
Computer Science, Information Systems
Claire Jean-Quartier, Miguel Rey Mazon, Mario Lovric, Sarah Stryeck
Summary: Research and development benefit from sharing knowledge bases and collaborative data utilization. However, most companies and organizations store their data in data silos, which hinders knowledge creation. To enable collaborative data sharing, public and private actors need to adopt a flexible approach and break data silos. This paper investigates the factors influencing cooperative data usage and explores the challenges of participating in cross-organizational data ecosystems, highlighting the technological and organizational requirements for collaborative data usage through an interview study with stakeholders from private and public organizations in the IDE@S project in Styria, Austria.
