Molecular bioenergetics deals with the construction, function and regulation of the powerhouses of life. The present overview sketches scenes and actors, farsighted goals and daring hypotheses, meticulous tool-making, painstaking benchwork, lucky discovery, serious scepticism, emphatic believing and strong characters with weak and others with hard arguments, told from a personal, admittedly limited, perspective. Bioenergetics will blossom further with the search focused on both where there is bright light for ever-finer detail and the obvious dark spots for surprise and discovery.
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Metabolic Flexibility and Essentiality of the Tricarboxylic Acid Cycle in .
ACS Infect Dis
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Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
The complete tricarboxylic acid (TCA) cycle, comprising a series of 8 oxidative reactions, occurs in most eukaryotes in the mitochondria and in many prokaryotes. The net outcome of these 8 chemical reactions is the release of the reduced electron carriers NADH and FADH, water, and carbon dioxide. The parasites of the .
View Article and Find Full Text PDFPlacental mitochondrial metabolic adaptation maintains cellular energy balance in pregnancy complicated by gestational hypoxia.
J Physiol
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.
The mechanisms that drive placental dysfunction in pregnancies complicated by hypoxia and fetal growth restriction remain poorly understood. Changes to mitochondrial respiration contribute to cellular dysfunction in conditions of hypoxia and have been implicated in the pathoaetiology of pregnancy complications, such as pre-eclampsia. We used bespoke isobaric hypoxic chambers and a combination of functional, molecular and imaging techniques to study cellular metabolism and mitochondrial dynamics in sheep undergoing hypoxic pregnancy.
View Article and Find Full Text PDFRationalizing protein-ligand interactions via the effective fragment potential method and structural data from classical molecular dynamics.
J Chem Phys
January 2025
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
The Effective Fragment Potential (EFP) method, a polarizable quantum mechanics-based force field for describing non-covalent interactions, is utilized to calculate protein-ligand interactions in seven inactive cyclin-dependent kinase 2-ligand complexes, employing structural data from molecular dynamics simulations to assess dynamic and solvent effects. Our results reveal high correlations between experimental binding affinities and EFP interaction energies across all the structural data considered. Using representative structures found by clustering analysis and excluding water molecules yields the highest correlation (R2 of 0.
View Article and Find Full Text PDFSympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of Oxytocin (OT)-elicited reductions of body weight gain and adiposity in male diet-induced obese rats.
Front Drug Deliv
December 2024
VA Puget Sound Health Care System, Office of Research and Development Medical Research Service, Department of Veterans Affairs Medical Center, Seattle, WA 98108, USA.
Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (T) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats.
View Article and Find Full Text PDFInsights on Bmi-1 therapeutic targeting in head and neck cancers.
Oncol Res
January 2025
LICIFO, Department of Restorative Sciences, Faculty of Dentistry, University of Costa Rica (HNSCC), San José, 11501, Costa Rica.
The B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) protein of the polycomb complex is an essential mediator of the epigenetic transcriptional silencing by the chromatin structure. It has been reported to be crucial for homeostasis of the stem cells and tumorigenesis. Though years of investigation have clarified Bmi-1's transcriptional regulation, post-translational modifications, and functions in controlling cellular bioenergetics, pathologies, and DNA damage response, the full potential of this protein with so many diverse roles are still unfulfilled.
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