Article
Immunology
Remi Hatinguais, Arnab Pradhan, Gordon D. Brown, Alistair J. P. Brown, Adilia Warris, Elena Shekhova
Summary: This study highlights the crucial role of mitochondrial ROS (mitoROS) in macrophage antifungal responses, specifically in the regulation of cytokine secretion through RET-mediated mitoROS production. Furthermore, NOX2 is demonstrated to be essential for regulating cytokine secretion by RET-associated mitoROS in response to infection with swollen conidia.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Natalia Baran, Alessia Lodi, Yogesh Dhungana, Shelley Herbrich, Meghan Collins, Shannon Sweeney, Renu Pandey, Anna Skwarska, Shraddha Patel, Mathieu Tremblay, Vinitha Mary Kuruvilla, Antonio Cavazos, Mecit Kaplan, Marc O. Warmoes, Diogo Troggian Veiga, Ken Furudate, Shanti Rojas-Sutterin, Andre Haman, Yves Gareau, Anne Marinier, Helen Ma, Karine Harutyunyan, May Daher, Luciana Melo Garcia, Gheath Al-Atrash, Sujan Piya, Vivian Ruvolo, Wentao Yang, Sriram Saravanan Shanmugavelandy, Ningping Feng, Jason Gay, Di Du, Jun J. Yang, Fieke W. Hoff, Marcin Kaminski, Katarzyna Tomczak, R. Eric Davis, Daniel Herranz, Adolfo Ferrando, Elias J. Jabbour, M. Emilia Di Francesco, David T. Teachey, Terzah M. Horton, Steven Kornblau, Katayoun Rezvani, Guy Sauvageau, Mihai Gagea, Michael Andreeff, Koichi Takahashi, Joseph R. Marszalek, Philip L. Lorenzi, Jiyang Yu, Stefano Tiziani, Trang Hoang, Marina Konopleva
Summary: The study reveals that T-ALL is commonly driven by activating mutations in NOTCH1, which directly relates to elevated OxPhos gene expression. Inhibition of OxPhos disrupts leukemia cell growth and induces metabolic reprogramming into glutaminolysis. Combining OxPhos blockade with inducible knock-down of glutaminase shows synthetic lethality in NOTCH1-mutated T-ALL mice.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Kalaiselvi Sivalingam, Thomas J. Cirino, Jay P. McLaughlin, Thangavel Samikkannu
Summary: HIV infection and cocaine consumption lead to oxidative stress and redox imbalance, causing neurodegeneration. The depletion of energy resources and glutathione synthetase in astrocytes results in the activation of AMPK and mitochondrial biogenesis, ultimately impacting Nrf transcription. Cocaine exacerbates these effects, worsening neurodegeneration.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Cell Biology
Xuan Wang, Yuting Ji, Jingyi Qi, Shuaishuai Zhou, Sitong Wan, Chang Fan, Zhenglong Gu, Peng An, Yongting Luo, Junjie Luo
Summary: Cervical cancer is a deadly disease in women, and mitochondrial-mediated ferroptosis (MMF) has been identified as a key factor in its development. By investigating the mitochondria transmembrane candidates, researchers discovered that mitochondrial carrier 1 (MTCH1) plays a central role in MMF in cervical cancers. MTCH1 deficiency disrupted mitochondrial oxidative phosphorylation and increased mitochondrial reactive oxygen species (ROS), leading to ferroptosis. Targeting MTCH1 in combination with Sorafenib effectively inhibited cervical cancer growth by inducing ferroptosis in a mouse xenograft model. These findings provide insights into the mechanisms of MMF and offer a potential therapeutic target for cervical cancer.
CELL DEATH & DISEASE
(2023)
Article
Nanoscience & Nanotechnology
Yifan Zhao, Bai Lv, Guanghe Xue, Yong Sun, Jie Cao
Summary: In this study, a nanosystem (named CyI & Met-Liposome, LCM) was designed to co-encapsulate the photosensitizer CyI and mitochondrial respiration inhibitor metformin (Met) for enhanced photodynamic therapy (PDT) efficiency. The results showed that LCM alleviated tumor hypoxia, enhanced PDT efficiency, and promoted antitumor immunity through oxygen-boosted PDT.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Ami Kobayashi, Toshihiko Takeiwa, Kazuhiro Ikeda, Satoshi Inoue
Summary: The mitochondrial electron transport chain (ETC) is crucial for energy production and drives various biochemical processes in eukaryotic cells through oxidative phosphorylation (OXPHOS). Recent studies have shown that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), transfer-RNA-derived fragments (tRFs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs), play important roles in regulating ETC and OXPHOS systems. This review highlights the emerging roles of ncRNAs in the regulation of mitochondrial ETC and OXPHOS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Shazma Bashir, Winston A. Morgan
Summary: The research findings indicate that the inhibition of mitochondrial function may be the key to the antipyretic and hypothermic properties of acetaminophen. By suppressing fatty acid uptake and oxidation, acetaminophen reduces mitochondrial function and subsequently lowers body temperature. These findings offer new insights for the development of new antipyretic drugs.
Article
Medicine, General & Internal
Ramana Vaka, Evangeline Deer, Mark Cunningham, Kristen M. McMaster, Kedra Wallace, Denise C. Cornelius, Lorena M. Amaral, Babbette LaMarca
Summary: Preeclampsia is associated with oxidative stress, placental ischemia, and autoantibodies to angiotensin II type I receptor. This study found that mitochondrial dysfunction plays a role in the pathophysiology of preeclampsia, particularly in affecting placental function. Antioxidants may not be an effective treatment for the oxidative stress in preeclampsia.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Liwei Wang, Qian Chen, Rui Ma, Bikui Zhang, Ping Yang, Ting Cao, Shimeng Jiao, Hui Chen, Chenquan Lin, Hualin Cai
Summary: Clozapine, while considered as a last resort for treatment-resistant schizophrenia, has limited efficacy in cognition improvement and can induce metabolic side effects that worsen cognitive impairment. The neurotoxic mechanisms of clozapine remain unclear. This study found that high concentrations of clozapine and AG205 resulted in cytotoxicity, reactive oxygen species accumulation, and mitochondrial membrane potential collapse in PC12 cells. Overexpression of progesterone receptor membrane component 1 (PGRMC1) reversed these toxic effects. Clozapine and AG205 also downregulated the expression of PGRMC1, glucagon-like peptide-1 receptor (GLP-1R), and mitofusin2 (Mfn2), which were restored by overexpressing PGRMC1. The findings suggest that PGRMC1 activation could be a promising therapeutic strategy for clozapine-induced neurotoxicity.
Article
Biology
Jingruo Zhang, Manuel A. Riquelme, Rui Hua, Francisca M. Acosta, Sumin Gu, Jean X. Jiang
Summary: This study reveals a new role of mitochondrial Cx43 and hemichannels in modulating mitochondrial function and homeostasis in bone osteocytes under oxidative stress. Through mediating K+, H+, and ATP transfer across the mitochondrial inner membrane and interacting with mitochondrial ATP synthase, mtCx43 hemichannels regulate mitochondrial ATP generation and contribute to the maintenance of mitochondrial redox levels in response to oxidative stress.
Article
Multidisciplinary Sciences
Ya-chun Han, Yu-ting Liu, Hao Zhang, Yong Xu, Jun Liu, Hong Chen, Na Song, Dong-lu Qin, Shikun Yang
Summary: This study investigated the effects and mechanism of Vitamin D receptor (VDR) signaling on arteriovenous fistula (AVF) endothelial cell injury. It was found that activation of VDR can alleviate venous endothelial cell dysfunction through inhibiting Pin1-mediated mitochondrial translocation of P66Shc and consequently reducing mitochondrial ROS.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Silvia Magalhaes-Novais, Jan Blecha, Ravindra Naraine, Jana Mikesova, Pavel Abaffy, Alena Pecinova, Mirko Milosevic, Romana Bohuslavova, Jan Prochazka, Shawez Khan, Eliska Novotna, Radek Sindelka, Radek Machan, Mieke Dewerchin, Erik Vlcak, Joanna Kalucka, Sona Stemberkova Hubackova, Ales Benda, Jermaine Goveia, Tomas Mracek, Cyril Barinka, Peter Carmeliet, Jiri Neuzil, Katerina Rohlenova, Jakub Rohlena
Summary: Mitochondrial oxidative phosphorylation (OXPHOS) not only generates ATP, but also supports autophagy to provide resistance against oxidative stress during cell quiescence.
Review
Biochemistry & Molecular Biology
Gurjit Kaur Bhatti, Anshika Gupta, Paras Pahwa, Naina Khullar, Satwinder Singh, Umashanker Navik, Shashank Kumar, Sarabjit Singh Mastana, Arubala P. Reddy, P. Hemachandra Reddy, Jasvinder Singh Bhatti
Summary: Mitochondria, the powerhouses of cells, play a vital role in maintaining normal cell functioning and human health. Dysfunctional mitochondria can lead to various diseases, affecting organs with high energy demand. Drugs or compounds targeting mitochondria are considered effective and safe for treating these diseases.
BIOMEDICAL JOURNAL
(2022)
Article
Endocrinology & Metabolism
Ioanna Papatheodorou, Marina Makrecka-Kuka, Janis Kuka, Edgars Liepinsh, Maija Dambrova, Antigone Lazou
Summary: Myocardial ischemia/reperfusion (I/R) injury is a leading cause of cardiac dysfunction and mortality worldwide. Activation of peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) protects the heart by reducing oxidative stress and inflammation. This study found that PPAR beta/delta activation improves mitochondrial fatty acid oxidation and respiratory function, leading to reduced myocardial ischemia/reperfusion injury.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Oncology
Yucheng Liu, Xinyan Wang, Wucheng Zhu, Zhongheng Sui, Xiangqing Wei, Yang Zhang, Jiansong Qi, Yanhong Xing, Wuyang Wang
Summary: This study reveals the mechanism by which TRPML1 inhibits autophagy to regulate apoptosis, involving disrupted mitochondrial turnover, elevated ROS, DNA damage, and p53 activation. These findings have potential clinical implications for treating melanoma and glioblastoma.
Article
Biochemical Research Methods
Shravan Sukumar, Xiaolei Zhu, Spencer S. Ericksen, Julie C. Mitchell
Article
Chemistry, Medicinal
Spencer S. Ericksen, Haozhen Wu, Huikun Zhang, Lauren A. Michael, Michael A. Newton, F. Michael Hoffmann, Scott A. Wildman
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2017)
Review
Oncology
Amruta P. Nayak, Arvinder Kapur, Lisa Barroilhet, Manish S. Patankar
Article
Chemistry, Medicinal
Shengchao Liu, Moayad Alnammi, Spencer S. Ericksen, Andrew F. Voter, Gene E. Ananiev, James L. Keck, F. Michael Hoffmann, Scott A. Wildman, Anthony Gitter
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2019)
Article
Biochemical Research Methods
Huikun Zhang, Spencer S. Ericksen, Ching-pei Lee, Gene E. Ananiev, Nathan Wlodarchak, Peng Yu, Julie C. Mitchell, Anthony Gitter, Stephen J. Wright, F. Michael Hoffmann, Scott A. Wildman, Michael A. Newton
PLOS COMPUTATIONAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Fan Zhang, Miao Zhao, Doug R. Braun, Spencer S. Ericksen, Jeff S. Piotrowski, Justin Nelson, Jian Peng, Gene E. Ananiev, Shaurya Chanana, Kenneth Barns, Jen Fossen, Hiram Sanchez, Marc G. Chevrette, Ilia A. Guzei, Changgui Zhao, Le Guo, Weiping Tang, Cameron R. Currie, Scott R. Rajski, Anjon Audhya, David R. Andes, Tim S. Bugni
Article
Biology
Peng Yu, Spencer Ericksen, Anthony Gitter, Michael A. Newton
Summary: This study addresses an important experimental design problem in early-stage drug discovery, focusing on prioritizing compounds for testing when little is known about the target protein. The Informer-based ranking (IBR) method is introduced as a solution, which selects a set of informer compounds and prioritizes the remaining compounds based on new bioactivity experiments. The Bayes Optimal Informer SEt (BOISE) method is proposed to efficiently solve this two-stage decision problem and outperforms other available methods in predicting protein-kinase inhibition and anticancer drug sensitivity.
Article
Chemistry, Medicinal
Junzhuo Liao, Xueqing Nie, Ilona Christy Unarta, Spencer S. Ericksen, Weiping Tang
Summary: This study demonstrates a method to distinguish native and non-native ternary complex poses based on the pose occupancy time. Using a specific heating scheme to accelerate pose departure, the native pose can be identified accurately. The dynamic scoring method takes into account the effect of entropy and is more reliable in determining the native pose.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Arvinder Kapur, Pooja Mehta, Aaron D. Simmons, Spencer S. Ericksen, Geeta Mehta, Sean P. Palecek, Mildred Felder, Zach Stenerson, Amruta Nayak, Jose Maria Ayuso Dominguez, Manish Patankar, Lisa M. Barroilhet
Summary: The Warburg effect, characterized by high glucose uptake and lactate release, is a hallmark of most cancers. Atovaquone, a mitochondrial complex III inhibitor, has been found to slow ovarian cancer growth and inhibit the proliferation of cancer stem cells both in vitro and in vivo. The drug is able to inhibit oxygen consumption and ATP production, and it alters several metabolic pathways. These findings provide mechanistic insights and preclinical data to support further investigation of atovaquone as a potential therapy for gynecologic cancers.
Article
Biology
Nicolas J. Wheeler, Kaetlyn T. Ryan, Kendra J. Gallo, Clair R. Henthorn, Spencer S. Ericksen, John D. Chan, Mostafa Zamanian
Summary: The development of direct acting macrofilaricides for the treatment of human filariases faces limitations in screening throughput due to the parasite life cycle. A multivariate screen using microfilariae identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of over 50%. Thorough characterization of compound activity on adult traits led to the discovery of five compounds with high potency against adults, but low potency or slow-acting microfilaricidal effects.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Medicinal
Moayad Alnammi, Shengchao Liu, Spencer Ericksen, Gene Ananiev, Andrew Voter, Song Guo, James Keck, F. Michael Hoffmann, Scott Wildman, Anthony Gitter
Summary: Traditional small-molecule drug discovery is time-consuming and costly. Modern machine-learning methods for virtual chemical screening show strong predictive power. This study validates the use of ligand-based virtual screening in large commercial libraries and demonstrates the superior performance of a random forest classifier.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Meeting Abstract
Oncology
Arvinder Kapur, Amruta P. Nayak, Thomas Beres, Kavya Rathi, Mildred Felder, Amani Gillette, Spencer Ericksen, Melissa Skala, Lisa Barroilhet, Manish S. Patankar