Article
Biochemistry & Molecular Biology
Jing Zhao, Xinyue Liu, Alan Blayney, Yumeng Zhang, Lauren Gandy, Paige Olivia Mirsky, Nathan Smith, Fuming Zhang, Robert J. Linhardt, Jianhan Chen, Christopher Baines, Stewart N. Loh, Chunyu Wang
Summary: The mitochondrial permeability transition pore (mPTP) plays crucial roles in various diseases. Cyclophilin D is confirmed as the only component of mPTP. Previous studies have reported that p53 interacts with CypD through its DNA-binding domain (DBD). However, this study found that the N-terminal domain (NTD) of p53 is the major binding site for CypD. The study provides insights into the dynamic interface between NTD and CypD.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Jose Perez, Rodrigo Ibarra-Garcia-Padilla, Maoping Tang, George A. Porter Jr, Gail V. W. Johnson, Rodrigo A. Quintanilla
Summary: The cleavage of tau protein by Caspase-3 negatively affects mitochondrial bioenergetics through the activation of mitochondrial permeability transition pore (mPTP), emphasizing the importance of this channel and its regulatory protein, cyclophilin D (CypD), in neuronal damage induced by tau pathology in Alzheimer's disease.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2024)
Review
Pharmacology & Pharmacy
Shaoyun Zhou, Qinwei Yu, Luyong Zhang, Zhenzhou Jiang
Summary: Mitochondria play multiple roles in cellular processes, acting as energy producers and biosynthetic centers. The opening of the mitochondrial permeability transition pore (mPTP) is a major contributor to mitochondrial dysfunction, leading to cellular damage or death. Cyclophilin D (CypD), a mitochondrial chaperone, has been identified as a key mediator of mPTP. Inhibiting CypD activity has shown to protect against diseases such as ischemia/reperfusion injury and neurodegenerative disorders.
CURRENT PHARMACEUTICAL DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Miguel Olivas-Aguirre, Liliana Torres-Lopez, Zeferino Gomez-Sandoval, Kathya Villatoro-Gomez, Igor Pottosin, Oxana Dobrovinskaya
Summary: The study demonstrated a synergistic cytotoxic effect of TAM and CBD against T-ALL cells. TAM targets CypD to inhibit mPTP formation, sensitizing T-ALL to CBD by altering mitochondrial Ca2+ homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Xavier R. Chapa-Dubocq, Keishla M. Rodriguez-Graciani, Nelson Escobales, Sabzali Javadov
Summary: Mitochondria, known as the powerhouse of the cell, regulate various cellular processes including ion homeostasis, energy production, and cell death. The inner mitochondrial membrane (IMM) plays a critical role in controlling mitochondrial metabolism and function. The volume of the mitochondrial matrix, regulated by ion transport mechanisms, influences IMM remodeling and can affect mitochondrial respiration and cell survival. Despite extensive research, the mechanisms underlying changes in matrix volume and IMM remodeling in response to energy and oxidative stressors remain poorly understood. This review summarizes previous studies and discusses the interplay between matrix volume regulation and IMM remodeling.
Article
Cell Biology
Igor Khaliulin, Raimondo Ascione, Leonid N. Maslov, Haitham Amal, M. Saadeh Suleiman
Summary: The study demonstrates that 8-Br can alleviate cardiac injury before regional ischemia or at the beginning of reperfusion, protecting the heart from reperfusion damage. This effect may be associated with the inhibition of MPTP through HKII binding to mitochondria.
Article
Cardiac & Cardiovascular Systems
Georgios Amanakis, Junhui Sun, Maria M. Fergusson, Shane McGinty, Chengyu Liu, Jeffery D. Molkentin, Elizabeth Murphy
Summary: The study demonstrates that C202 plays a crucial role in the binding of CypD to PTP, with its oxidation state potentially regulating the opening of mitochondrial permeability transition pore. Mutating C202 reduces ischemia/reperfusion injury, and C202 is found to be S-nitrosylated during ischemic preconditioning.
CARDIOVASCULAR RESEARCH
(2021)
Review
Cell Biology
Ibrahim Damilare Boyenle, Abdulquddus Kehinde Oyedele, Abdeen Tunde Ogunlana, Aishat Folashade Adeyemo, Faith Sunday Oyelere, Olateju Balikis Akinola, Temitope Isaac Adelusi, Leonard Ona Ehigie, Adeola Folasade Ehigie
Summary: The mitochondrial permeability transition pore (MPTP) is a pore formed on the inner mitochondrial membrane under calcium overload and oxidative stress, which can cause cell death and has physiological significance. Various models of MPTP have been proposed, with F1Fo ATPase being the most debated candidate protein. Cyclophilin D (CyPD) is widely accepted as the positive regulator of MPTP, but no drug candidate as its inhibitor has emerged.
Article
Endocrinology & Metabolism
Astrid L. Basse, Marianne Agerholm, Jean Farup, Emilie Dalbram, Joachim Nielsen, Niels Ortenblad, Ali Altintas, Amy M. Ehrlich, Thomas Krag, Santina Bruzzone, Morten Dall, Roldan M. de Guia, Jonas B. Jensen, Andreas B. Moller, Anders Karlsen, Michael Kjaer, Romain Barres, John Vissing, Steen Larsen, Niels Jessen, Jonas T. Treebak
Summary: The study showed that NAMPT is crucial for maintaining cellular Ca2+ homeostasis and skeletal muscle development, which is vital for juvenile survival. Through analysis of skeletal muscle-specific Nampt KO mice, it was found that NAMPT plays a critical role in these processes.
MOLECULAR METABOLISM
(2021)
Review
Chemistry, Medicinal
Annamaria Haleckova, Ondrej Benek, Lucie Zemanova, Rafael Dolezal, Kamil Musilek
Summary: This review provides an overview of current knowledge on CypD inhibitors, with a focus on the in vitro activity of small-molecule compounds, their selectivity for CypD, and their binding mode within the enzyme's active site. Approaches for improving the molecular design of CypD inhibitors are also discussed.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Balazs Koszegi, Gabor Balogh, Zoltan Berente, Anett Vranesics, Edit Pollak, Laszlo Molnar, Aniko Takatsy, Viktoria Poor, Matyas Wahr, Csenge Antus, Krisztian Eros, Laszlo Vigh, Ferenc Gallyas, Maria Peter, Balazs Veres
Summary: Recent studies have shown that the absence of cyclophilin D (CypD) affects glucose and lipid metabolism, resulting in lipid-specific alterations. Our analysis of CypD-/- mice compared to wild-type mice revealed significant changes in lipid species in liver and plasma samples. This study highlights the potential long-term therapeutic implications of CypD inhibition for various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sergey Sosunov, Arnav Bhutada, Zoya Niatsetskaya, Anatoly Starkov, Vadim Ten
Summary: Hypothermia is a standard treatment for hypoxic-ischemic brain injury, but its therapeutic mechanisms are not well understood. This study found that brain mitochondria at a lower temperature exhibited greater resistance to calcium-induced pore opening. The improvement in mitochondrial tolerance to this process may contribute to the neuroprotective effects of hypothermia.
Review
Biochemistry & Molecular Biology
Gabriele Coluccino, Valentina Pia Muraca, Alessandra Corazza, Giovanna Lippe
Summary: Mitochondrial dysfunction is crucial in many complex diseases. Understanding the role of the mitochondrial matrix protein CyPD in regulating cell death and its involvement in neurodegenerative disorders, particularly Alzheimer's Disease and Parkinson's Disease, can provide new therapeutic targets. CyPD is involved in regulating the permeability transition pore in the inner mitochondrial membrane, and its dysregulated opening can lead to cell death. Additionally, CyPD interacts with various biochemical pathways. Exploring the post-translational modifications of CyPD can enhance our understanding. Development of CyPD-specific inhibitors holds promise for the treatment of these complex diseases.
Article
Multidisciplinary Sciences
Erminia Donnarumma, Michael Kohlhaas, Elodie Vimont, Etienne Kornobis, Thibault Chaze, Quentin Giai Gianetto, Mariette Matondo, Maryse Moya-Nilges, Christoph Maack, Timothy Wai
Summary: The protein MTFP1 plays a crucial role in the control of cardiac structure and function. Knockout of MTFP1 in mice leads to the development of heart disease and remodeling of the mitochondria and heart. This study reveals new functions of MTFP1 in regulating bioenergetic efficiency and cell death sensitivity, highlighting its importance in preventing heart disease.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Kunqiao Hong, Qian Yang, Gen Liu, Hu Qiu, Baoping Yu
Summary: Acute acalculous cholecystitis (AAC) is a disease with acute onset, rapid progression, high mortality, and various complications. Cyclophilin D (CypD) plays a proinflammatory role by regulating the opening of the mitochondrial permeability transition pore. Inhibiting the activity of CypD can reduce oxidative stress and apoptosis, thereby alleviating the symptoms of the disease.
CURRENT MOLECULAR MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Rob Wallis, Mayel Gharanei, Helen Maddock
JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS
(2015)
Article
Cardiac & Cardiovascular Systems
Afthab Hussain, Ahmed Mayel Gharanei, Aarondeep Singh Nagra, Helen L. Maddock
CARDIOVASCULAR DRUGS AND THERAPY
(2014)
Review
Medicine, Research & Experimental
Hardip Sandhu, Helen Maddock
Article
Toxicology
Kate L. Harvey, Afthab Hussain, Helen L. Maddock
TOXICOLOGICAL SCIENCES
(2014)
Article
Toxicology
Mayel Gharanei, Afthab Hussain, Rob S. James, Omar Janneh, Helen Maddock
TOXICOLOGY IN VITRO
(2014)
Article
Multidisciplinary Sciences
Sophie Fletcher, Helen Maddock, Rob S. James, Rob Wallis, Mayel Gharanei
SCIENTIFIC REPORTS
(2020)
Article
Biochemical Research Methods
Mayel Gharanei, Sanam Shafaattalab, Sarabjit Sangha, Marvin Gunawan, Zachary Laksman, Leif Hove-Madsen, Glen F. Tibbits
Summary: The discovery and utilization of human-induced pluripotent stem cells (hiPSCs) have played a crucial role in investigating the pathophysiology of cardiovascular diseases. These cells can be generated from patients, edited on genome level, and differentiated into various cell types, providing a platform for regenerative medicine, disease modeling, drug testing, and tissue generation. Advancements have been made in differentiating patient-specific atrial cardiac myocytes (hiPSC-aCM) and atrial engineered heart tissue (aEHT), which have helped in understanding the mechanisms of atrial-specific diseases and evaluating the effectiveness of atrial-selective drugs. However, the immature phenotype of hiPSC-CMs compared to adult CMs remains a limitation.
Article
Cardiac & Cardiovascular Systems
Refik Kuburas, Mayel Gharanei, Irmgard Haussmann, Helen Maddock, Hardip Sandhu
Summary: This study investigates the effects of metformin on sunitinib-induced cytotoxicity and finds that metformin can attenuate the negative effects of sunitinib on the heart.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
Article
Physiology
Ben J. Lee, Emma L. Emery-Sinclair, Richard W. A. Mackenzie, Afthab Hussain, Lee Taylor, Rob S. James, C. Douglas Thake
EXTREME PHYSIOLOGY & MEDICINE
(2014)