The first component of the mitochondrial electron transport chain is respiratory complex I. Several high-resolution structures of complex I from different species have been resolved. However, despite these significant achievements, the mechanism of redox-coupled proton pumping remains elusive. Here, we combined atomistic docking, molecular dynamics simulations, and site-directed mutagenesis on respiratory complex I from Yarrowia lipolytica to identify a quinone (Q)-binding site on its surface near the horizontal amphipathic helices of ND1 and NDUFS7 subunits. The surface-bound Q makes stable interactions with conserved charged and polar residues, including the highly conserved Arg72 from the NDUFS7 subunit. The binding and dynamics of a Q molecule at the surface-binding site raise interesting possibilities about the mechanism of complex I, which are discussed.
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http://dx.doi.org/10.1002/1873-3468.14346 | DOI Listing |
PLoS One
January 2025
Cardiovascular Outcomes Research Laboratories (CORELAB), University of California, Los Angeles, Los Angeles, CA, United States of America.
Purpose: Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been noted to face increased cancer incidence. Yet, the impact of concomitant renal dysfunction on acute outcomes following elective surgery for cancer remains to be elucidated.
Methods: All adult hospitalizations entailing elective resection for lung, esophageal, gastric, pancreatic, hepatic, or colon cancer were identified in the 2016-2020 National Inpatient Sample.
PLoS One
January 2025
Department of Computer Science, University College London, London, United Kingdom.
Complex biological systems undergo sudden transitions in their state, which are often preceded by a critical slowing down of dynamics. This results in longer recovery times as systems approach transitions, quantified as an increase in measures such as the autocorrelation and variance. In this study, we analysed paediatric patients in intensive care for whom mechanical ventilation was discontinued through removal of the endotracheal tube (extubation).
View Article and Find Full Text PDFEur J Pediatr
January 2025
Pediatric Hematology and Oncology, Liv Hospital, Gaziantep, Turkey.
Unlabelled: Spondyloenchondrodysplasia (SPENCD) is a rare genetic disorder characterized with skeletal dysplasia, immune dysregulation, and neurological impairment. Patients diagnosed with SPENCD at a single pediatric hematology center were included in the study. The patients' clinical characteristics, symptoms at presentation, imaging and laboratory results, and genetic analysis results were collected retrospectively from their files.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, 9 Dongdan 3rd Alley, Beijing, 100730, China.
Bullous pemphigoid (BP) is a debilitating autoimmune skin blistering disease, characterized by the deposition of specific autoantibodies at the dermal-epidermal junction. This leads to an inflammatory cascade involving the activation of complement proteins, mast cell degranulation, immune cell recruitment, and the release of proteases by granulocytes. While several cytokines and signaling pathways have been implicated in the pathogenesis of BP, the precise mechanism behind autoantibody production remains unclear.
View Article and Find Full Text PDFCell Mol Life Sci
January 2025
State Key Laboratory of Reproductive Medicine and Offspring Health, Department of Histology and Embryology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.
Defects in motile cilia and flagella lead to motile ciliopathies, including primary ciliary dyskinesia (PCD), which manifests as multi-organ dysfunction such as hydrocephalus, infertility, and respiratory issues. CFAP65 variants are a common cause of male infertility, but its localization and function have remained unclear. In this study, we systematically evaluated CFAP65's role using Cfap65 knockout mice and human patients with CFAP65 variants.
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