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Comparative functional analysis reveals differential nucleotide sensitivity between human and mouse UCP1.
Acta Physiol (Oxf)
September 2024
Chair for Molecular Nutritional Medicine, TUM School of Life Sciences, Research Department of Molecular Life Sciences, Technical University of Munich, Freising, Germany.
Aim: Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non-complexed purine nucleotides inhibit this fatty acid-induced activity of UCP1.
View Article and Find Full Text PDFProtective effects of 2,4-dinitrophenol in okadaic acid-induced cellular model of Alzheimer's disease.
Biochim Biophys Acta Mol Basis Dis
August 2024
CNC-UC - Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal; CIBB - Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal; Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-370 Coimbra, Portugal.
Alzheimer's disease (AD) research started several decades ago and despite the many efforts employed to develop new treatments or approaches to slow and/or revert disease progression, AD treatment remains an unsolved issue. Knowing that mitochondria loss of function is a central hub for many AD-associated pathophysiological processes, there has been renewed interest in exploring mitochondria as targets for intervention. In this perspective, the present study was aimed to investigate the possible beneficial effects of 2,4 dinitrophenol (DNP), a mitochondrial uncoupler agent, in an in vitro model of AD.
View Article and Find Full Text PDFCritical roles of tubular mitochondrial ATP synthase dysfunction in maleic acid-induced acute kidney injury.
Apoptosis
June 2024
Department of Anatomy, College of Medicine, Kaohsiung Medical University, 100, Shih-Chuan 1St Road, Kaohsiung, 80708, Taiwan.
Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking.
View Article and Find Full Text PDFUncoupling Protein: A Complete Sequence, Activity, and Role in Response to Oxidative Stress.
Int J Mol Sci
August 2023
Department of Bioenergetics, Faculty of Biology, Adam Mickiewicz University, Uniwersytetu Poznanskiego 6, 61-614 Poznan, Poland.
Uncoupling proteins (UCPs) are mitochondrial inner membrane transporters that mediate free-fatty-acid-induced, purine-nucleotide-inhibited proton leak into the mitochondrial matrix, thereby uncoupling respiratory substrate oxidation from ATP synthesis. The aim of this study was to provide functional evidence that the putative gene of the free-living protozoan amoeba, , encodes the mitochondrial protein with uncoupling activity characteristic of UCPs and to investigate its role during oxidative stress. We report the sequencing and cloning of a complete coding sequence, its phylogenetic analysis, and the heterologous expression of AcUCP in the strain Measurements of mitochondrial respiratory activity and membrane potential indicate that the heterologous expression of AcUCP causes AcUCP-mediated uncoupling activity.
View Article and Find Full Text PDFMolecular determinants of inhibition of UCP1-mediated respiratory uncoupling.
Nat Commun
May 2023
Institut de Biologie Physico-Chimique, Fondation Edmond de Rothschild, Paris, 75005, France.
Brown adipose tissue expresses uncoupling protein 1 (UCP1), which dissipates energy as heat, making it a target for treating metabolic disorders. Here, we investigate how purine nucleotides inhibit respiration uncoupling by UCP1. Our molecular simulations predict that GDP and GTP bind UCP1 in the common substrate binding site in an upright orientation, where the base moiety interacts with conserved residues R92 and E191.
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