Article
Biochemistry & Molecular Biology
Ljudmila S. Khailova, Vladimir S. Krasnov, Roman S. Kirsanov, Lyudmila B. Popova, Vadim N. Tashlitsky, Elena A. Kotova, Yuri N. Antonenko
Summary: The fungicide fluazinam exhibits a cyclic pattern of protonophoric uncoupling activity in isolated rat liver mitochondria, which is likely due to glutathione conjugation catalyzed by glutathione-S-transferase. This uncoupling activity is transient in liver mitochondria but stable in kidney and heart mitochondria, possibly due to higher mitochondrial GST activity in the liver.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Toxicology
Zuzana Hatokova, Andrea Evinova, Peter Racay
Summary: STF-083010 is an inhibitor of IRE1α endonuclease activity, which is involved in the activation of IRE1α-XBP1 axis in the unfolded protein response after ER stress. It exhibits antitumor activity and increases the sensitivity of tumor cells to other neoplastic agents. Additionally, it has hepatoprotective effects in various models of liver injury and steatohepatitis. Our study reveals that STF-083010 has a significant impact on mitochondrial functions, which is not dependent on its ability to inhibit IRE1α endonuclease activity.
TOXICOLOGY IN VITRO
(2023)
Article
Cell Biology
Xavier R. Chapa-Dubocq, Keishla M. Rodriguez-Graciani, Jorge Garcia-Baez, Alyssa Vadovsky, Jason N. Bazil, Sabzali Javadov
Summary: This study elucidates the crucial role of OPA1 in the regulation of mitochondrial fusion and maintenance of structural integrity. The cleavage of OPA1, induced by calcium swelling in the presence of Myls22 and TPEN, plays a role in response to stress by maintaining mitochondrial bioenergetics.
Article
Biochemistry & Molecular Biology
Hazirah Hassan, Fazaine Zakaria, Suzana Makpol, Norwahidah Abdul Karim
Summary: The study sheds light on the potential link between mitochondrial dysfunction and autism spectrum disorder (ASD), with findings indicating significantly dysregulated mitochondrial function in ASD patients compared to healthy controls, particularly in terms of oxidative phosphorylation (OXPHOS) and mitochondrial membrane potential.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ljubava D. Zorova, Irina B. Pevzner, Ljudmila S. Khailova, Galina A. Korshunova, Marina A. Kovaleva, Leonid I. Kovalev, Marina V. Serebryakova, Denis N. Silachev, Roman V. Sudakov, Savva D. Zorov, Tatyana I. Rokitskaya, Vasily A. Popkov, Egor Y. Plotnikov, Yuri N. Antonenko, Dmitry B. Zorov
Summary: The homeostasis of transmembrane potential of hydrogen ions in mitochondria is crucial for normal mitochondrial functioning. Mild reduction of membrane potential is recommended in pathological conditions, while maintaining ATP production at sufficient levels for normal cell functioning. Chemical agents and natural proteins such as UCP family proteins, adenine nucleotide translocator, and dicarboxylate carrier have been found to provide uncoupling. This study demonstrates that the butyl ester of rhodamine 19, C4R1, binds to components of the mitochondrial ATP synthase complex through electrostatic interaction, resulting in effective uncoupling. The more hydrophobic derivative C12R1 shows weaker uncoupling activity due to poor binding to mitochondria. Mass spectrometry confirms C4R1 binding to the beta-subunit of mitochondrial ATP synthase, and molecular docking suggests a binding site on the interface between the alpha- and beta-subunits, close to the anionic amino acid residues of the beta-subunit. The association of uncoupling effect with binding suggests that the ATP synthase complex can induce uncoupling.
Article
Pharmacology & Pharmacy
Huan Yang, Wanda van der Stel, Randy Lee, Caroline Bauch, Sam Bevan, Paul Walker, Bob van de Water, Erik H. J. Danen, Joost B. Beltman
Summary: Mitochondria are the main bioenergetic organelles of cells and exposure to chemicals targeting mitochondria generally results in toxicity. Different mitochondrial respiration inhibitors have varying effects on mitochondrial membrane potential, and mathematical modeling can help understand these dynamics. Additionally, incorporating pharmacokinetic decay into the model can improve the fit for certain compounds, showing a complex interplay between pharmacokinetics and MMP dynamics within mitochondria.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Olivier Lurette, Hala Guedouari, Jordan L. Morris, Rebeca Martin-Jimenez, Julie-Pier Robichaud, Genevieve Hamel-Cote, Mehtab Khan, Nicholas Dauphinee, Nicolas Pichaud, Julien Prudent, Etienne Hebert-Chatelain
Summary: The architecture of mitochondria is regulated by the tyrosine kinase Src, which affects mitochondrial morphology independently of mitochondrial size, cellular respiration, or ATP levels. This study highlights a novel function for Src in the control of mitochondrial dynamics.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, Research & Experimental
Yoshikazu Kuwahara, Kazuo Tomita, Mehryar Habibi Roudkenar, Amaneh Mohammadi Roushandeh, Yusuke Urushihara, Kento Igarashi, Akihiro Kurimasa, Tomoaki Sato
Summary: The study revealed that modulation of mitochondrial function is implicated in the radioresistance phenotype of cancer cells, and radioresistance of clinically relevant radioresistant cells is reversible. Further studies are needed to clarify the mechanisms underlying cancer cell radioresistance.
Review
Biochemistry & Molecular Biology
Hagai Rottenberg
Summary: It is widely reported that the mitochondrial membrane potential, increment ψm, is reduced in aging animals. It was recently suggested that the lower increment ψm in aged animals modulates mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased increment ψm in C. elegans increased lifespan. The activation of the voltage-gated mitochondrial permeability transition pore (mPTP) is the main cause of the increase in depolarized mitochondria in aged cells, inhibiting oxidative phosphorylation, releasing calcium and mROS, and depleting NAD(+), thereby accelerating degenerative diseases and aging. The reported lifespan extension by artificially generated increment ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Elizabeth Murphy, Julia Liu
Summary: Cardiomyocytes have a high density of mitochondria, which play a crucial role in energy production and cellular functions. The regulation of mitochondrial calcium and reactive oxygen species is important in the development of cardiovascular disease.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Kristina Zymone, Raimondas Benetis, Darius Trumbeckas, Ingrida Baseviciene, Sonata Trumbeckaite
Summary: Flavonols and their glycosides have been found to affect mitochondrial respiration and possess antioxidant properties. This study investigated the effects of quercetin and its glycosides on mitochondrial function, showing that they can increase respiration rates and decrease the production of H2O2. Quercetin displayed the highest activity, while the sugar residue significantly diminished its activity.
Article
Biochemistry & Molecular Biology
Agata Kaczmarek, Anna Katarzyna Wronska, Mieczyslawa Irena Bogus
Summary: This study investigates the role of mitochondria in insect cell apoptosis induced by Conidiobolus coronatus. The results show that during fungal infection, insect mitochondria undergo various changes, including loss of membrane potential, megachannel formation, disturbances in respiration, and changes in oxygen consumption. Additionally, the study confirms the translocation of cytochrome c-like protein, higher activation of caspase-9-like protein, and calcium overload in mitochondria. The findings suggest that apoptosis in insects involves similar processes as in mammalian cells, indicating evolutionary conservation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Deyamira Matuz-Mares, Martin Gonzalez-Andrade, Minerva Georgina Araiza-Villanueva, Maria Magdalena Vilchis-Landeros, Hector Vazquez-Meza
Summary: The article highlights the importance of calcium in cellular processes and discusses how cells buffer calcium by compartmentalizing it into mitochondria and the endoplasmic reticulum. It further explores the relationship between calcium homeostasis imbalance and neurodegenerative diseases, summarizing some therapeutic approaches for these diseases.
Review
Biochemistry & Molecular Biology
David G. Nicholls
Summary: This review examines the mechanisms underlying non-shivering thermogenesis in brown adipose tissue mediated by UCP1, emphasizing the experimental evidence and physiological constraints. It also discusses the nature of endogenous proton leak and evaluates the troubled history of putative novel uncoupling proteins UCP2 and UCP3.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
(2021)
Article
Toxicology
David S. Umbaugh, Nga T. Nguyen, Hartmut Jaeschke, Anup Ramachandran
Summary: Mitochondrial morphology changes play a critical role in acetaminophen (APAP) hepatotoxicity, with distinct morphologies corresponding to differences in mitochondrial respiratory function and polarization. These changes in morphology are dose-dependent and can be reversible or irreversible depending on the severity of APAP overdose.
TOXICOLOGICAL SCIENCES
(2021)
