Editorial Material
Biochemistry & Molecular Biology
Frederic Bouillaud
Summary: This article examines the consequences of sulfide oxidation by mitochondrial sulfide quinone reductase in mammalian cells. The oxidation of sulfide helps to avoid self-poisoning and has a lower ATP/O-2 ratio compared to other mitochondrial substrates. It increases cellular oxygen consumption and impacts the cellular ATP/ADP ratio.
Review
Biochemistry & Molecular Biology
Ke Cao, Jie Xu, Wenli Cao, Xueqiang Wang, Weiqiang Lv, Mengqi Zeng, Xuan Zou, Jiankang Liu, Zhihui Feng
Summary: Mitochondrial succinate dehydrogenase (SDH) is an enzyme complex that plays a crucial role in regulating mitochondrial metabolism and human health. Recent studies have revealed the dynamic involvement of SDH assembly process in various diseases. Perturbation of SDH assembly in different tissues can lead to distinct pathophysiological changes, highlighting the importance of understanding the intricate SDH assembly process in human health and diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Adam J. Rauckhorst, Liping Yu, Brian D. Fink, Ritu Som, Eric B. Taylor, William I. Sivitz
Summary: Under low inner mitochondrial membrane potential, oxaloacetate accumulates in organelles and inhibits succinate dehydrogenase, leading to decreased complex II-energized respiration. This process is more active in muscle than in interscapular brown adipose tissue (IBAT) mitochondria. In IBAT mitochondria, oxaloacetate is decarboxylated to pyruvate.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2023)
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
Biochemistry & Molecular Biology
Max Holzknecht, Lena Guerrero-Navarro, Michele Petit, Eva Albertini, Elisabeth Damisch, Anna Simonini, Fernando Schmitt, Walther Parson, Heidelinde Fiegl, Alexander Weiss, Pidder Jansen-Duerr
Summary: FAHD1 is upregulated in breast cancer tissues and is crucial for the survival of basal breast cancer cells BT-20. Knocking down FAHD1 reduces succinate dehydrogenase activity in breast cancer cell lines MCF-7 and BT-20, leading to reduced proliferation in MCF-7 cells cultured with glutamine as the carbon source. Additionally, FAHD1 is involved in glutaminolysis in the mitochondria.
Article
Biochemistry & Molecular Biology
Sui Lay, Xavier Pearce, Oana Sanislav, Paul Robert Fisher, Sarah Jane Annesley
Summary: Mitochondrial Complex II is composed of four core subunits and mutations in any of these subunits can result in lowered Complex II activity. However, mutations in different subunits are associated with distinct patterns of clinical disease. In this study, knockdown of individual Complex II subunits in Dictyostelium discoideum revealed specific phenotypic defects and mitochondrial dysfunction associated with SdhA knockdown. These defects were mediated by the chronic activation of AMP-activated protein kinase.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Xin Tang, Shuang Zhao, Jieqiong Liu, Xiameng Liu, Xinqi Sha, Changgao Huang, Lulu Hu, Shixiu Sun, Yuanqing Gao, Hongshan Chen, Zhiren Zhang, Dongjin Wang, Yuexi Gu, Shaoliang Chen, Liansheng Wang, Aihua Gu, Feng Chen, Jun Pu, Xin Chen, Bo Yu, Liping Xie, Zhengrong Huang, Yi Han, Yong Ji
Summary: This study identified a novel species of GSNOR localized in mitochondria and found that mitochondrial GSNOR plays a crucial role in maintaining mitochondrial homeostasis through ANT1 denitrosylation, providing a potential novel therapeutic target for heart failure.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Pavla Stankova, Otto Kucera, Eva Peterova, Moustafa Elkalaf, David Rychtrmoc, Jan Melek, Miroslav Podhola, Veronika Zubanova, Zuzana Cervinkova
Summary: The study found that after consuming a Western-style diet for 30 weeks, mice showed reduced succinate-activated respiration, decreased SDH activity, reduced expression of the SDH activator sirtuin 3 and SDH subunits, and increased succinate levels. The gene and protein expression of SUCNR1 also decreased in the livers of mice fed the diet, but no signs of oxidative damage were observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Hiran A. Prag, Michael P. Murphy, Thomas Krieg
Summary: In the context of myocardial infarction, the burst of superoxide generated by reverse electron transport (RET) at complex I in mitochondria is a crucial trigger for damage during ischaemia/reperfusion (I/R) injury. Here we outline the necessary conditions for superoxide production by RET at complex I and how it can occur during reperfusion. In addition, we explore various pathways that are implicated in generating the conditions for RET to occur and suggest potential therapeutic strategies to target RET, aiming to achieve cardioprotection.
BASIC RESEARCH IN CARDIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Camila Cimadamore-Werthein, Stephany Jaiquel Baron, Martin S. King, Roger Springett, Edmund R. S. Kunji
Summary: The mitochondrial ADP/ATP carrier plays a crucial role in oxidative phosphorylation by importing ADP into the mitochondrial matrix and exporting ATP. Recent studies have revealed that the carrier functions as a monomer with a single substrate binding site and operates with a ping-pong kinetic mechanism. These findings reconcile the discrepancy between the previous assumptions and provide insights into the alternating access mechanism of the carrier.
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)
Review
Physiology
Rachel M. Handy, Graham P. Holloway
Summary: Impairments in peripheral tissue insulin signaling, caused by a high-lipid environment and increased mitochondrial reactive oxygen species production, are believed to contribute to insulin resistance and type 2 diabetes. However, physical inactivity can also promote insulin resistance through alternative mechanisms, such as a reduction in protein synthesis. Mitochondrial biology plays a crucial role in the interaction between physical (in)activity, lipid metabolism, and insulin signaling.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Cameron A. Schmidt
Summary: Mitochondria play a central role in the physiology and survival of eukaryotic cells. Small molecules that modulate mitochondrial metabolism can have complex systemic effects. This article reviews the effects of prescription drugs on mitochondrial metabolism, discusses qualitative models of drug-mitochondria interactions, and highlights specific drug classes for further discussion.
BIOSCIENCE REPORTS
(2022)
Article
Medicine, Research & Experimental
Ana Cristina S. Bombaca, Leonardo A. Silva, Otavio Augusto Chaves, Lorrainy S. da Silva, Juliana M. C. Barbosa, Ari M. da Silva, Aurelio B. B. Ferreira, Rubem F. S. Menna-Barreto
Summary: This study introduces a novel anti-protozoan drug N4 and its mechanism of action against Trypanosoma cruzi, showing high activity in all parasite stages and indicating it as a potential alternative treatment for Chagas disease. The results presented here may serve as a good starting point for the development of alternative treatments for Chagas disease and for understanding the mechanism of naphthoimidazoles in T. cruzi.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Sanjana Mahadev Bhat, Jane Q. Yap, Oscar A. Ramirez-Ramirez, Philippe Delmotte, Gary C. Sieck
Summary: In this study, a quantitative histochemical technique was used to measure the activity of succinate dehydrogenase (SDH) in the inner mitochondrial membrane of human airway smooth muscle (hASM) cells. The technique involved measuring the change in optical density (OD) caused by the reduction of a reaction indicator (NBT) using a confocal microscope. This method was found to be rigorous, reproducible, and reliable for measuring mitochondrial function in individual cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Dominic G. Roy, Jocelyn Chen, Victoria Mamane, Eric H. Ma, Brejnev M. Muhire, Ryan D. Sheldon, Tatiana Shorstova, Rutger Koning, Radia M. Johnson, Ekaterina Esaulova, Kelsey S. Williams, Sebastian Hayes, Mya Steadman, Bozena Samborska, Amanda Swain, Audrey Daigneault, Victor Chubukov, Thomas P. Roddy, William Foulkes, J. Andrew Pospisilik, Marie-Claude Bourgeois-Daigneault, Maxim N. Artyomov, Michael Witcher, Connie M. Krawczyk, Catherine Larochelle, Russell G. Jones
Article
Endocrinology & Metabolism
William I. Sivitz, Lawrence S. Phillips, Deborah J. Wexler, Stephen P. Fortmann, Anne W. Camp, Margaret Tiktin, Magalys Perez, Jacqueline Craig, Priscilla A. Hollander, Andrea Cherrington, Vanita R. Aroda, Meng Hee Tan, Jonathan Krakoff, Neda Rasouli, Nicole M. Butera, Naji Younes
Article
Cell Biology
Michael A. Petrie, Arpit Sharma, Eric B. Taylor, Manish Suneja, Richard K. Shields
PHYSIOLOGICAL GENOMICS
(2020)
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)
Editorial Material
Multidisciplinary Sciences
Arpit Sharma
Review
Cell Biology
Hannah J. Smith, Arpit Sharma, William B. Mair
DEVELOPMENTAL CELL
(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
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
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
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.
Article
Multidisciplinary Sciences
Yan Yan, Somnath Mukherjee, Kaleeckal G. Harikumar, Timothy S. Strutzenberg, X. Edward Zhou, Kelly Suino-Powell, Ting-Hai Xu, Ryan D. Sheldon, Jared Lamp, Joseph S. Brunzelle, Katarzyna Radziwon, Abigail Ellis, Scott J. Novick, Irving E. Vega, Russell G. Jones, Laurence J. Miller, H. Eric Xu, Patrick R. Griffin, Anthony A. Kossiakoff, Karsten Melcher
Summary: AMPK regulates cellular metabolism by modulating AL phosphorylation and accessibility, with ATP inhibiting its activity when levels are low. Researchers have developed antibodies and analyzed structures to reveal the mechanism by which adenine nucleotides and pharmacological agonists regulate AMPK activity.
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)