54,683 research outputs found
A first--order irreversible thermodynamic approach to a simple energy converter
Several authors have shown that dissipative thermal cycle models based on
Finite-Time Thermodynamics exhibit loop-shaped curves of power output versus
efficiency, such as it occurs with actual dissipative thermal engines. Within
the context of First-Order Irreversible Thermodynamics (FOIT), in this work we
show that for an energy converter consisting of two coupled fluxes it is also
possible to find loop-shaped curves of both power output and the so-called
ecological function against efficiency. In a previous work Stucki [J.W. Stucki,
Eur. J. Biochem. vol. 109, 269 (1980)] used a FOIT-approach to describe the
modes of thermodynamic performance of oxidative phosphorylation involved in
ATP-synthesis within mithochondrias. In that work the author did not use the
mentioned loop-shaped curves and he proposed that oxidative phosphorylation
operates in a steady state simultaneously at minimum entropy production and
maximum efficiency, by means of a conductance matching condition between
extreme states of zero and infinite conductances respectively. In the present
work we show that all Stucki's results about the oxidative phosphorylation
energetics can be obtained without the so-called conductance matching
condition. On the other hand, we also show that the minimum entropy production
state implies both null power output and efficiency and therefore this state is
not fulfilled by the oxidative phosphorylation performance. Our results suggest
that actual efficiency values of oxidative phosphorylation performance are
better described by a mode of operation consisting in the simultaneous
maximization of the so-called ecological function and the efficiency.Comment: 20 pages, 7 figures, submitted to Phys. Rev.
Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency
Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)–encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromosome 3q containing elongation factor G1 (EFG1), which encodes a mitochondrial translation factor. Sequencing of EFG1 revealed a mutation affecting a conserved residue of the guanosine triphosphate (GTP)–binding domain. These results define a new class of gene defects underlying disorders of oxidative phosphorylation
A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis
During late gestation, villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence in mice that Yin Yang 1 (Yy1) is crucial for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration might function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find that necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests that it might contribute to neonatal gastrointestinal disorders
RNAase III-Type Enzyme Dicer Regulates Mitochondrial Fatty Acid Oxidative Metabolism in Cardiac Mesenchymal Stem Cells
Cardiac mesenchymal stem cells (C-MSC) play a key role in maintaining normal cardiac function under physiological and pathological conditions. Glycolysis and mitochondrial oxidative phosphorylation predominately account for energy production in C-MSC. Dicer, a ribonuclease III endoribonuclease, plays a critical role in the control of microRNA maturation in C-MSC, but its role in regulating C-MSC energy metabolism is largely unknown. In this study, we found that Dicer knockout led to concurrent increase in both cell proliferation and apoptosis in C-MSC compared to Dicer floxed C-MSC. We analyzed mitochondrial oxidative phosphorylation by quantifying cellular oxygen consumption rate (OCR), and glycolysis by quantifying the extracellular acidification rate (ECAR), in C-MSC with/without Dicer gene deletion. Dicer gene deletion significantly reduced mitochondrial oxidative phosphorylation while increasing glycolysis in C-MSC. Additionally, Dicer gene deletion selectively reduced the expression of β-oxidation genes without affecting the expression of genes involved in the tricarboxylic acid (TCA) cycle or electron transport chain (ETC). Finally, Dicer gene deletion reduced the copy number of mitochondrially encoded 1,4-Dihydronicotinamide adenine dinucleotide (NADH): ubiquinone oxidoreductase core subunit 6 (MT-ND6), a mitochondrial-encoded gene, in C-MSC. In conclusion, Dicer gene deletion induced a metabolic shift from oxidative metabolism to aerobic glycolysis in C-MSC, suggesting that Dicer functions as a metabolic switch in C-MSC, which in turn may regulate proliferation and environmental adaptation
Role of the Intracellular pH in the Metabolic Switch between Oxidative Phosphorylation and AerobicGlycolysis - Relevance to Cancer
Cellular energy in the form of ATP can be produced
through oxidative phosphorylation and through
glycolysis. Since oxidative phosphorylation requires
oxygen and generates ATP more efficiently than
glycolysis, it has been assumed for many years that
the presence or absence of oxygen determines that
cells generate energy through oxidative
phosphorylation or through glycolysis. Although cells
must activate glycolysis in the absence of oxygen to
produce ATP, it is now accepted that they can activate
both glycolysis and oxidative phosphorylation in the
presence of oxygen. In fact, normal proliferating cells
and tumor cells are known to have a high glycolytic
activity in the presence of adequate oxygen levels, a
phenomenon known as aerobic glycolysis or the
Warburg effect. Recent observations have
demonstrated that the activation of aerobic glycolysis
plays a major role in carcinogenesis and tumor growth.
Understanding the mechanisms involved in the
metabolic switch between oxidative phosphorylation
and aerobic glycolysis may therefore be important for
the development of potential preventive and
therapeutic interventions. In this article, we discuss the
role of the intracellular pH in the metabolic switch
between oxidative phosphorylation and aerobic
glycolysis. We propose that, in the presence of
adequate oxygen levels, the intracellular pH may play
a key role in determining the way cells obtain energy,
an alkaline pH driving aerobic glycolysis and an acidic
pH driving oxidative phosphorylation
Correlation of structure and function in the oxidative phosphorylation system of submitochondrial particles
1. After the centrifugation of sonicated heavy beef heart mitochondria at 75, 000 × g for 10 minutes, the supernatant was centrifuged at 144, 000 × g for 30 minutes. The residue was revealed being composed of
vesicular inner membrane fragments (ETPH), about 600 to 1000 Å. in diameter, showing a morphological homogeneity and a high capacity of oxidative phosphorylation. 2. The Pia ratio of the ETPH in the presence of succinate and of NADH2 was 1.68 and 2.54, respectively, and the corrected Pia value for O2 gas equilibrium was 1. 01 and 1.40, respectively.
3. The capacity of oxidative phosphorylation in ETPH fraction was parallel to the activity of the oligomycin. sensitive ATPase in these fractions. 4. The P/0 ratio of ETPH was decreased to about 50 % by hypotonic
treatment. The decrease of P/0 ratio was restored to the level of about 90 % by incubating the ETPH with ATP and BSA. In the instance where the P/0 ratio was low level in the hypotonic medium, the surface structure of ETPH was observed as a swollen form and the head pieces
of the elementary particles were clearly observed in contrast to the solid surface structure of ETPH in the isotonic medium. 5. The P/0 ratio of ETPH was decreased to about 60 % by relatively severe sonication, and after separating the residue from the supernatant, that of the residue decreased further to about 40 %. The P/0 ratio of the residue was restored to the level before the separation on the addition of the supernatant containing oligomycin-insensitive ATPase. 6. A discussion was made on the correlation between the surface structure and the activities at terminal phosphorylation step of ETPH
after the simple physico-chemical treatment.</p
Changes of fatty acid metabolism and oxidative phosphorylation of rat liver mitochondria during 3'-Me-DAB feeding
Respiration, activity of oleate oxidation and composition of the total fatty acids of rat liver were investigated in 3'-Me-DAB feeding. 1. Oxidative phosphorylation of rat liver mitochondria decreased temporarily at relatively earlier stages (about 2 to 3 weeks) in 3'-Me-DAB feeding. 2. The activity of oleate oxidation of rat liver mitochondria decreased rapidly to about one third of that in control groups after the start of 3'-Me-DAB feeding. 3. In the composition of the total fatty acids of rat liver, the proportion of oleic acid increased in 3'-Me-DAB groups. 4. Unknown octadecamonoenoic acid was observed in liver mitochondria of rat fed on 3'-Me-DAB. 5. Proportions of oleic and palmitoleic acids in liver tumors and mitochondria of liver tumors induced by 3'-Me-DAB feeding increased remarkably in contrast with decrease in those of palmitic and eicosapolyenoic acids. 6. A possibility was discussed about how higher level of oleate in the liver cells in azo dye feeding may be concerned with the tumor induction.</p
A physical model of cell metabolism
Cell metabolism is characterized by three fundamental energy demands: to sustain cell maintenance, to trigger aerobic fermentation and to achieve maximum metabolic rate. The transition to aerobic fermentation and the maximum metabolic rate are currently understood based on enzymatic cost constraints. Yet, we are lacking a theory explaining the maintenance energy demand. Here we report a physical model of cell metabolism that explains the origin of these three energy scales. Our key hypothesis is that the maintenance energy demand is rooted on the energy expended by molecular motors to fluidize the cytoplasm and counteract molecular crowding. Using this model and independent parameter estimates we make predictions for the three energy scales that are in quantitative agreement with experimental values. The model also recapitulates the dependencies of cell growth with extracellular osmolarity and temperature. This theory brings together biophysics and cell biology in a tractable model that can be applied to understand key principles of cell metabolism
The effect of reducing ATP levels on reorientation of the secondary palate
The force for directing palate shelf reorientation appears to be associated with elements of the presumptive hard palate (Brinkley & Vickerman, 1979; Bulleit & Zimmerman, 1985). The palatal elements that mediate this process do not require palate cells to be metabolically active for expression of the force. This contention was demonstrated using an in vitro system that allows substantial reorientation of the hard palate to occur. ATP levels were reduced by treatment with metabolic inhibitors and the degree of reorientation was measured 1 h following pretreatment with inhibitors. Treatment of cultured embryonic heads under anoxic conditions with 2,4-dinitrophenol or KCN had noeffect on the degree of reorientation occurring in vitro. These agents reduced ATP levels by 71 % and 62 %, respectively. Treatment of cultured heads with 2-deoxy-D-glucose under anoxia also had no effect on reorientation. This treatment reduced ATP levels in embryonic heads by 92–94%. A similar reduction was observed if ATP levels were measured in palate tissue alone. The treatment of cultured heads with 2-deoxy-D-glucose and anoxia not only reduced levels of ATP but also reduced CTP, GTP and UTP. These results indicate that palate shelf reorientation is independent of cellular metabolic activity and supports the hypothesis that reorientation is dependent on a pre-existing infrastructure within the palate shelves
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