Article
Multidisciplinary Sciences
Ivan Menendez-Montes, Salim Abdisalaam, Feng Xiao, Nicholas T. Lam, Shibani Mukherjee, Luke I. Szweda, Aroumougame Asaithamby, Hesham A. Sadek
Summary: Mitochondrial utilization of fatty acids induces a significant increase in ROS detection at the chromatin level, indicating that mitochondrial metabolic perturbations directly alter the nuclear redox status, with chromatin being particularly sensitive to the prooxidant effect of FA utilization by the mitochondria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Patrizia Bottoni, Alessandro Pontoglio, Salvatore Scara, Luisa Pieroni, Andrea Urbani, Roberto Scatena
Summary: Mitochondrial bioenergetics play an important role in pathophysiology, especially as unintended targets of different drugs. PPAR ligands, a class of drugs that activate Peroxisome Proliferator-Activated Receptors, were found to inhibit NADH coenzyme Q reductase and induce complex mitochondrial oxidative metabolism damage. This damage affects not only ATP synthesis but also respiratory control ratio, spare respiratory capacity, coupling efficiency, oxidative stress, and mitochondrial structural damage.
Article
Chemistry, Multidisciplinary
Marta Vranas, Daniel Wohlwend, Danye Qiu, Stefan Gerhardt, Christian Trncik, Mehrosh Pervaiz, Kevin Ritter, Stefan Steimle, Antonio Randazzo, Oliver Einsle, Stefan Gunther, Henning J. Jessen, Alexander Kotlyar, Thorsten Friedrich
Summary: This study reports the specific action and structure of a novel inhibitor NADH-OH on respiratory complex I, revealing its regulatory role in mitochondrial ROS generation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Kang Liu, Zheng Zhang, Rujia Liu, Jie P. Li, Dechen Jiang, Rongrong Pan
Summary: The study presents a new nanoelectrode-based pipette architecture for the in-depth study of single cells. The architecture allows the isolation and monitoring of a small region of mitochondrial membranes in a living cell using click chemistry. The study also provides direct evidence for the noninvolvement of glutathione peroxidase 4 in mitochondria during RSL3-induced reactive oxygen species (ROS) generation at the single-mitochondrion level.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
James H. Schofield, Zachary T. Schafer
Summary: The relationship between mitophagy and ROS production is complex and not fully understood. This review discusses mtROS generation and their detrimental effects on cellular viability, along with the cellular defense mechanisms against oxidative stress. Furthermore, the prominent mechanisms governing mitophagy induction that bear on oxidative stress are explored.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Review
Biochemistry & Molecular Biology
Javier Florido, Cesar Rodriguez-Santana, Laura Martinez-Ruiz, Alba Lopez-Rodriguez, Dario Acuna-Castroviejo, Iryna Rusanova, Germaine Escames
Summary: ROS are highly reactive molecules that regulate important signaling pathways. Tumor cells have altered redox balance compared to normal cells, making them susceptible to anti-tumoral therapy targeting ROS levels and antioxidant system capacity. Melatonin has potential as an innovative cancer treatment, but its mechanism of action remains unclear, limiting its clinical applications.
Article
Biochemistry & Molecular Biology
Jae-Sung Kim, Ye-Ram Kim, Sein Jang, Sang Geon Wang, Euni Cho, Seok-Jun Mun, Hye-In Jeon, Hyo-Keun Kim, Sun-Joon Min, Chul-Su Yang
Summary: Rubicon interacts with p22phox to regulate ROS production in immune cells. Mito-TIPTP inhibits the interaction between Rubicon and p22phox, enhancing mitochondrial function and showing therapeutic effects in colitis models. This suggests Mito-TIPTP as a potential therapeutic agent for colitis by targeting the Rubicon-p22phox interaction.
Article
Pharmacology & Pharmacy
Fei Liu, Longhui Yuan, Lan Li, Jingchao Yang, Jingping Liu, Younan Chen, Jie Zhang, Yanrong Lu, Yujia Yuan, Jingqiu Cheng
Summary: Senescence of bone marrow mesenchymal stem cells (BMSCs) is a leading cause of osteoporosis. SIRT3, an essential NAD-dependent histone deacetylase, is associated with BMSC senescence-mediated bone degradation and mitochondrial/heterochromatic disturbance. S-sulfhydration of cysteine residues enhances SIRT3 activity. The underlying mechanism of SIRT3 S-sulfhydration on mitochondrial/heterochromatic homeostasis in BMSC senescence is unknown. The study demonstrates the role of SIRT3 S-sulfhydration in stabilizing heterochromatin and mitochondrial homeostasis in counteracting BMSC senescence, providing a potential target for the treatment of degenerative bone diseases.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Food Science & Technology
Xiaoting Sun, Yuanyuan Li, Yanqi Lin, Yuanyuan Mei, Lingli Lin, Kuo-Ting Ho, Jialin Zhan, Chaoxiang Chen, Jun Zeng, Jian Li, Jingwen Liu, Guiling Li
Summary: This study found that curcumin can enhance cellular antioxidant capacity and mitochondrial function by downregulating miR-22-3p and targeting CRLS1 gene.
JOURNAL OF FUNCTIONAL FOODS
(2023)
Article
Microbiology
Melissa A. Sleda, Zhu-Hong Li, Ranjan Behera, Baihetiya Baierna, Catherine Li, Jomkwan Jumpathong, Satish R. Malwal, Makoto Kawamukai, Eric Oldfield, Silvia N. J. Moreno
Summary: This study investigates the synthesis of polyprenyl diphosphate in Toxoplasma gondii and identifies the enzyme TgCoq1 as a key player in this process. The growth of TgCoq1 mutants is impaired, but can be rescued by complementation with a homologous gene or a related enzyme. Additionally, a bisphosphonate is found to inhibit T. gondii growth, which can be reversed by supplementation with long-chain ubiquinone. Importantly, the bisphosphonate also protects mice against lethal T. gondii infection.
Article
Cell Biology
Marisol Cano, Sayantan Datta, Lei Wang, Tongyun Liu, Miguel Flores-Bellver, Mira Sachdeva, Debasish Sinha, James T. Handa
Summary: Studies have shown that Nrf2 deficiency affects mitochondrial antioxidant response and exacerbates mitochondrial dysfunction, leading to cell death. Furthermore, Nrf2 indirectly supplies NADPH through influencing PPP and IDH shuttle activity, which also impacts the pathobiology of AMD.
Article
Medicine, Research & Experimental
Wanessa M. C. Awata, Juliano V. Alves, Rafael M. Costa, Ariane Bruder-Nascimento, Shubhnita Singh, Gabriela S. Barbosa, Carlos Renato Tirapelli, Thiago Bruder-Nascimento
Summary: This study found that ethanol-induced vascular dysfunction may be mediated by RAAS activation, mitochondrial dysfunction, and mitochondrial reactive oxygen species (mtROS). Inhibition of the AT(1) receptor can prevent vascular hypercontractility, mitochondrial dysfunction, and mtROS production, as well as restore the bioavailability of nitric oxide and hydrogen peroxide.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Immunology
Nan-Nan Liang, Ying Zhao, Yue-Yue Guo, Zhi-Hui Zhang, Lan Gao, De-Xin Yu, De-Xiang Xu, Shen Xu
Summary: This study found that mitochondria-derived reactive oxygen species (ROS) contribute to renal cell ferroptosis during lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Inhibition of ferroptosis and scavenging of mitochondrial ROS with specific inhibitors, ferrostatin-1 and MitoQ, respectively, attenuated renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage, and renal cell death. These findings suggest that mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Sara Ranjbarvaziri, Kristina B. Kooiker, Mathew Ellenberger, Giovanni Fajardo, Mingming Zhao, Alison Schroer Vander Roest, Rahel A. Woldeyes, Tiffany T. Koyano, Robyn Fong, Ning Ma, Lei Tian, Gavin M. Traber, Frandics Chan, John Perrino, Sushma Reddy, Wah Chiu, Joseph C. Wu, Joseph Y. Woo, Kathleen M. Ruppel, James A. Spudich, Michael P. Snyder, Kevin Contrepois, Daniel Bernstein
Summary: The study found that metabolic signaling disruption and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM, highlighting potential new drug targets for mitigating the disease by improving metabolic function and reducing mitochondrial injury.
Review
Immunology
Miranda D. Chavez, Hubert M. Tse
Summary: Mitochondrial dysfunction and oxidative stress are associated with T cell-mediated autoimmune diseases, and targeting metabolic pathways can inhibit autoreactive T cell activation. Increasing the requirements of Tregs for ROS and oxidative phosphorylation can promote self-tolerance and inhibit the activity of autoreactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Endocrinology & Metabolism
Siming Liu, Joseph A. Promes, Mikako Harata, Akansha Mishra, Samuel B. Stephens, Eric B. Taylor, Anthony J. Burand, William I. Sivitz, Brian D. Fink, James A. Ankrum, Yumi Imai
Article
Biochemistry & Molecular Biology
Brian Fink, Lawrence Coppey, Eric Davidson, Hanna Shevalye, Alexander Obrosov, Pratik Rajesh Chheda, Robert Kerns, William Sivitz, Mark Yorek
FREE RADICAL RESEARCH
(2020)
Article
Endocrinology & Metabolism
Ionut Bebu, Barbara H. Braffett, David Schade, William Sivitz, John I. Malone, Rodica Pop-Busui, Gayle M. Lorenzi, Pearl Lee, Victoria R. Trapani, Amisha Wallia, William H. Herman, John M. Lachin
Editorial Material
Endocrinology & Metabolism
Mark Yorek
JOURNAL OF DIABETES RESEARCH
(2020)
Article
Chemistry, Medicinal
Chaitanya A. Kulkarni, Brian D. Fink, Bettine E. Gibbs, Pratik R. Chheda, Meng Wu, William Sivitz, Robert J. Kerns
Summary: The study identified an inert mitochondria-targeting carrier by modifying the structure of TPP+, which successfully eliminated uncoupling activity, prevented dissipation of mitochondrial membrane potential, and did not negatively affect cargo delivery to mitochondria.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Alexander Strom, Klaus Strassburger, Martin Schmuck, Hanna Shevalye, Eric Davidson, Fariba Zivehe, Gidon Boenhof, Rudolph Reimer, Bengt-Frederik Belgardt, Thomas Fleming, Barbara Biermann, Volker Burkart, Karsten Muessig, Julia Szendroedi, Mark A. Yorek, Ellen Fritsche, Peter P. Nawroth, Michael Roden, Dan Ziegler
Summary: The lack of effective treatments for diabetic sensorimotor polyneuropathy has led to the search for new strategies to combat or prevent the condition. This study found that reduced serum magnesium levels and increased plasma methylglyoxal levels were associated with the development of the condition. Additionally, the interaction between magnesium and methylglyoxal played a role in methylglyoxal-dependent nerve dysfunction, with magnesium supplementation showing a neuroprotective effect.
MOLECULAR METABOLISM
(2021)
Article
Pharmacology & Pharmacy
Brian D. Fink, Liping Yu, Lawrence Coppey, Alexander Obrosov, Hanna Shevalye, Robert J. Kerns, Mark A. Yorek, William Sivitz
Summary: Our research shows that mitoQ has a positive impact on HF-fed obese rats by reducing liver lipid hydroperoxides and improving glycemia. However, it has little effect on diabetic rats. Additionally, mitoQ reduces liver fat and hydroperoxide levels but does not improve liver function.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Endocrinology & Metabolism
Lawrence Coppey, Alexander Obrosov, Hanna Shevalye, Eric Davidson, William Paradee, Mark A. Yorek
Summary: The study found that treating type 2 diabetic mice with menhaden oil can improve deficits related to diabetic peripheral neuropathy (DPN), with more significant effects observed in transgenic mice, indicating a potential protective role of menhaden oil in DPN. Targeting pathways to increase the production of anti-inflammatory metabolites of omega-3 PUFA may be an effective approach in developing treatments for DPN.
JOURNAL OF DIABETES RESEARCH
(2021)
Article
Medicine, Research & Experimental
Akansha Mishra, Siming Liu, Joseph Promes, Mikako Harata, William Sivitz, Brian Fink, Gourav Bhardwaj, Brian T. O'Neill, Chen Kang, Rajan Sah, Stefan Strack, Samuel Stephens, Timothy King, Laura Jackson, Andrew S. Greenberg, Frederick Anokye-Danso, Rexford S. Ahima, James Ankrum, Yumi Imai
Summary: Research shows that PLIN2 plays an important role in preserving insulin secretion, beta cell metabolism, and mitochondrial function in beta cells under nutritional stress.
Review
Nutrition & Dietetics
Scott M. Ebert, Blake B. Rasmussen, Andrew R. Judge, Sarah M. Judge, Lars Larsson, Ronald C. Wek, Tracy G. Anthony, George R. Marcotte, Matthew J. Miller, Mark A. Yorek, Adrian Vella, Elena Volpi, Jennifer Stern, Matthew D. Strub, Zachary Ryan, John J. Talley, Christopher M. Adams
Summary: Activating transcription factor 4 (ATF4) is a multifunctional protein that regulates transcription and is involved in various cellular responses. Most of our knowledge about ATF4 comes from studies conducted in cultured cells, with limited understanding of its in vivo role. This review provides an overview of the basic biology of ATF4 and focuses on its role in mammalian skeletal muscle fibers.
JOURNAL OF NUTRITION
(2022)
Review
Endocrinology & Metabolism
Mark Yorek
Summary: Animal models have played a crucial role in exploring the etiology and potential treatments for diabetic peripheral neuropathy. However, the complexity of the disease and the differences between type 1 and type 2 diabetes pose challenges in successful translation of treatment strategies from animal studies to human clinical trials. Various mechanisms have been identified, including hyperglycemia, insulin resistance, hyperlipidemia, oxidative and inflammatory stress, dysregulation of protein kinase C and hexosamine pathways, and decreased neurotrophic support.
CURRENT DIABETES REVIEWS
(2022)
Article
Cell Biology
Ritu Som, Brian D. Fink, Liping Yu, William I. Sivitz
Summary: Previous research showed that mitochondria with low membrane potential in skeletal muscle and interscapular brown adipose tissue can accumulate oxaloacetate to inhibit complex II respiration. Further studies on mice with different inner membrane potential in brown adipose tissue verify this mechanism and its physiological significance.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Endocrinology & Metabolism
Lawrence Coppey, Eric Davidson, Hanna Shevalye, Alexander Obrosov, Michael Torres, Mark A. Yorek
DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY
(2020)