Advances in systems biology and whole-cell modelling demand increasingly comprehensive mathematical models of cellular biochemistry. Such models require the development of simplified representations of specific processes which capture essential biophysical features but without unnecessarily complexity. Recently there has been renewed interest in thermodynamically-based modelling of cellular processes. Here we present an approach to developing of simplified yet thermodynamically consistent (hence physically plausible) models which can readily be incorporated into large scale biochemical descriptions but which do not require full mechanistic detail of the underlying processes. We illustrate the approach through development of a simplified, physically plausible model of the mitochondrial electron transport chain and show that the simplified model behaves like the full system.
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http://dx.doi.org/10.1016/j.jtbi.2020.110223 | DOI Listing |
J Vis Exp
January 2025
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Henry and Allison McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Harvard Medical School;
A method to quantitate the stabilization of Mitochondria-Associated endoplasmic reticulum Membranes (MAMs) in a 3-dimensional (3D) neural model of Alzheimer's disease (AD) is presented here. To begin, fresh human neuro progenitor ReN cells expressing β-amyloid precursor protein (APP) containing familial Alzheimer's disease (FAD) or naïve ReN cells are grown in thin (1:100) Matrigel-coated tissue culture plates. After the cells reach confluency, these are electroporated with expression plasmids encoding red fluorescence protein (RFP)-conjugated mitochondria-binding sequence of AKAP1(34-63) (Mito-RFP) that detects mitochondria or constitutive MAM stabilizers MAM 1X or MAM 9X that stabilize tight (6 nm ± 1 nm gap width) or loose (24 nm ± 3 nm gap width) MAMs, respectively.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Huai'an Hospital Affiliated to Yangzhou University, The Fifth People's Hospital of Huai'an), 1 Huaihe East Road, Huaiyin District, Huai'an City, Jiangsu Province, China.
Ginkgolide B (GB) is a bioactive constituent found in Ginkgo biloba leaves that has been long recognized as a protective agent against many neurological disorders. Our study aimed to examine the effect of GB in an in vitro Parkinson's disease (PD) model and to investigate its neuroprotective mechanism as a primary objective. SK-N-SH cells were challenged with 1-methyl-4-phenylpyridinium (MPP) to act as a PD-like model of neuronal damage.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 573 Xujiahui Road, Huangpu District, Shanghai 200025, China.
Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice and cells, both of which exhibited dramatic mitochondrial changes.
View Article and Find Full Text PDFJ Med Chem
January 2025
Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot 010021, People's Republic of China.
In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand ()-based Ru(II) complexes with general formula [(Ru()(-cymene)]·Cl (-), characterized by H NMR, C NMR, UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand's orientation around the Ru(II) center. All 12 of these 12 complexes were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy of , , and was demonstrated by reduced mitochondrial membrane potential, impaired proliferative capacity, and disrupted redox homeostasis, along with enhanced apoptosis through caspase-3 activation and downregulation of Bcl-2 expression.
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