The H+-ATP synthase: A gate to ROS-mediated cell death or cell survival

This article is part of a Special Issue entitled: 18th European Bioenergetic ConferenceCellular oxidative stress results from the increased generation of reactive oxygen species and/or the dysfunction of the antioxidant systems. Most intracellular reactive oxygen species derive from superoxide radical although the majority of the biological effects of reactive oxygen species are mediated by hydrogen peroxide. In this contribution we overview the major cellular sites of reactive oxygen species production, with special emphasis in the mitochondrial pathways. Reactive oxygen species regulate signaling pathways involved in promoting survival and cell death, proliferation, metabolic regulation, the activation of the antioxidant response, the control of iron metabolism and Ca2 + signaling. The reversible oxidation of cysteines in transducers of reactive oxygen species is the primary mechanism of regulation of the activity of these proteins. Next, we present the mitochondrial H+-ATP synthase as a core hub in energy and cell death regulation, defining both the rate of energy metabolism and the reactive oxygen species-mediated cell death in response to chemotherapy. Two main mechanisms that affect the expression and activity of the H+-ATP synthase down-regulate oxidative phosphorylation in prevalent human carcinomas. In this context, we emphasize the prominent role played by the ATPase Inhibitory Factor 1 in human carcinogenesis as an inhibitor of the H+-ATP synthase activity and a mediator of cell survival. The ATPase Inhibitory Factor 1 promotes metabolic rewiring to an enhanced aerobic glycolysis and the subsequent production of mitochondrial reactive oxygen species. The generated reactive oxygen species are able to reprogram the nucleus to support tumor development by arresting cell death. Overall, we discuss the cross-talk between reactive oxygen species signaling and mitochondrial function that is crucial in determining the cellular fateWork in the authors’ laboratory was supported by grants from the Ministerio de Educación y Ciencia (BFU2010-18903), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII and by Comunidad de Madrid (S/2011-BMD-2402), Spain. The CBMSO receives an institutional grant from Fundación Ramón Arece

miR-127-5p targets the 3'UTR of human β-F1-ATPase mRNA and inhibits its translation

IMW and IMR are the recipients of pre-doctoral fellowships from the Plan de Formación de Profesorado Universitario (AP2007-03035) from the Ministerio de Educación and JAE-CSIC, respectively. The work was supported by grants from the Ministerio de Educación y Ciencia (BFU2010- 18903), by the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII and by Comunidad de Madrid (S2011/BMD-2402), Spain. The CBMSO receives an institutional grant from Fundación Ramón Arece

AMPK and GCN2-ATF4 signal the repression of mitochondria in colon cancer cells

Reprogramming of energetic metabolism is a phenotypic trait of cancer in which mitochondrial dysfunction represents a key event in tumour progression. In the present study, we show that the acquisition of the tumour-promoting phenotype in colon cancer HCT116 cells treated with oligomycin to inhibit ATP synthase is exerted by repression of the synthesis of nuclear-encoded mitochondrial proteins in a process that is regulated at the level of translation. Remarkably, the synthesis of glycolytic proteins is not affected in this situation. Changes in translational control of mitochondrial proteins are signalled by the activation of AMPK (AMP-activated protein kinase) and the GCN2 (general control non-derepressible 2) kinase, leading also to the activation of autophagy. Changes in the bioenergetic function of mitochondria are mimicked by the activation of AMPK and the silencing of ATF4 (activating transcription factor 4). These findings emphasize the relevance of translational control for normal mitochondrial function and for the progression of cancer. Moreover, they demonstrate that glycolysis and oxidative phosphorylation are controlled at different levels of gene expression, offering the cell a mechanistic safeguard strategy for metabolic adaptation under stressful conditions.</jats:p

Biodiversity and distribution of macroinfauna assemblages on sandy beaches along the Gulf of Cadiz (SW Spain)

In the current study, the macroinfauna communities inhabiting 12 sandy beaches along the Spanish coast of the Gulf of Cadiz were describe in order to characterize their unexplored biodiversity, their zonation patterns and their environmental features. A total of 66 macroinfauna taxa were recorded on 12 sandy beaches, ranging from 4 to 33 species. Density reached 848 individual per m2. The individual zonation pattern ranged from two to three zones, regardless of the morphodynamic state. A common zonation pattern of the whole set of beaches was established, comprising three across-shore biological zones. Generally, the supralittoral zone was typified by the air-breathing amphipod Talitrus saltator and coleopterans; the middle zone was dominated by true intertidal species, such as Haustoriidae amphipods (Haustorius arenarius), Cirolanidae isopods (Eurydice affinis), Spionidae polychaetes (Scolelepis spp.) and nemerteans; and the lower or sublittoral zone was typified by Pontoporeiidae amphipods, mysids and spionid polychaetes. Sediment moisture, average grain size, organic matter content and elevation were the main predictor variables of zonation patterns. We used the conservation and recreation potential indices to show how this information can be useful for coastal management. Most beaches studied show a score above 5 on the conservation index, so the beaches have a reasonable potential for conservation management.En el presente estudio, se describen las comunidades de macroinfauna de doce playas arenosas de la costa española del Golfo de Cádiz con el objetivo de caracterizar su biodiversidad, sus patrones de zonación, y sus características ambientales. Un total de 66 taxones de macroinfauna fueron registrados en las playas de estudio, oscilando entre 4 y 33 especies, mientras que la densidad total fue de 848 individuos por m2. El patrón de zonación individual varió de dos a tres zonas, independientemente del estado morfodinámico de la playa. Se estableció un patrón de zonación común de todo el conjunto de playas, formado por tres zonas biológicas. En general, la zona supralitoral fue tipificada por el anfípodo Talitrus saltator y diversas familias de coleópteros. La zona media fue dominada por verdaderas especies intermareales, como anfípodos de la famila Haustoriidae (Haustorius arenarius), isópodos cirolánidos (Eurydice affinis), poliquetos (Scolelepis spp.) y nemertinos. La zona sublitoral se caracterizó por anfípodos de la familia Pontoporeiidae, misidáceos y poliquetos espiónidos. La humedad del sedimento, el tamaño medio de grano, el contenido en materia orgánica y la elevación fueron las principales variables influyentes en los patrones de zonación. Por último, toda esta información fue integrada para la aplicación de los índices de Conservación y Recreación, para mostrar cómo esta información puede ser útil para la gestión costera. La mayoría de las playas mostraron una puntuación superior a 5 en el Índice de Conservación, indicando un razonable potencial para la conservación.Gobierno de Andalucía P09- HUM-4717Ministerio de Educación AP-2009-390

In-flame soot quantification of diesel sprays under sooting/non-sooting critical conditions in an optical engine

[EN] Because of the challenge of meeting stringent emissions regulations for internal combustion engines, some advanced low temperature combustion modes have been raised in recent decades to improve combustion efficiency. Therefore, detailed understanding and capability for accurate prediction of in-flame soot processes under such low sooting conditions are becoming necessary. Nowadays, a lot of investigations have been carried out to quantify in-flame soot in Diesel sprays under high sooting conditions by means of different optical techniques. However, no information of soot quantification can be found for sooting/non-sooting critical conditions. In current study, the instantaneous soot production in a two-stroke optical engine under low sooting conditions has been measured by means of a Diffused back-illumination extinction technique (DBI) and two-color method (2C) simultaneously. The fuels used were n-dodecane and n-heptane, which have been injected separately though two different injectors equipped with single-hole nozzles. A large cycle-to-cycle variation on soot production can be observed under such operating conditions, however the in-cylinder heat release traces were quite repeatable. It is the same with the well-known trends of soot amount to operating conditions that the probability of sooting cycles increases with higher ambient temperature, higher ambient density and lower injection pressure. Both techniques present a pretty good agreement on soot amount when the peak of KL value is close to 1. However, the KL value of two-color method becomes bigger than that of DBI and the difference increases with lower sooting conditions.This study was partially funded by the Natural Science Foundation of China (No. 51876083), China Postdoctoral Science Foundation (2018M642176) and High-tech Research Key laboratory of Zhenjiang (SS2018002)Xuan, T.; Pastor, JV.; García-Oliver, JM.; García Martínez, A.; He, Z.; Wang, Q.; Reyes, M. (2019). In-flame soot quantification of diesel sprays under sooting/non-sooting critical conditions in an optical engine. Applied Thermal Engineering. 149:1-10. https://doi.org/10.1016/j.applthermaleng.2018.11.112S11014

Degradation of IF1 controls energy metabolism during osteogenic differentiation of stem cells

Differentiation of human mesenchymal stem cells (hMSCs) requires the rewiring of energy metabolism. Herein, we demonstrate that the ATPase inhibitory factor 1 (IF1) is expressed in hMSCs and in prostate and colon stem cells but is not expressed in the differentiated cells. IF1 inhibits oxidative phosphorylation and regulates the activity of aerobic glycolysis in hMSCs. Silencing of IF1 in hMSCs mimics the metabolic changes observed in osteocytes and accelerates cellular differentiation. Activation of IF1 degradation acts as the switch that regulates energy metabolism during differentiation. We conclude that IF1 is a stemness marker important for maintaining the quiescence stateThis work was supported by grants from the Ministerio de Educación y Ciencia (BFU2010-18903), the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), ISCIII, and Comunidad de Madrid (S2011/BMD-2402), Spai

Functional statistical techniques applies to vine leaf water content

P. 1116-1122A statistical analysis of functional data, obtained as reflectance values measured using a hyperspectral sensor, was used to determine water content in vine leaves. Our study was conducted using a sample of 80 vine leaves whose water content was determined by calculating the weight difference between leaves before and after drying in an oven.S

Overexpression of the ATPase Inhibitory Factor 1 Favors a Non-metastatic Phenotype in Breast Cancer

Partial suppression of mitochondrial oxidative phosphorylation and the concurrent activation of aerobic glycolysis is a hallmark of proliferating cancer cells. Overexpression of the ATPase inhibitory factor 1 (IF1), an in vivo inhibitor of the mitochondrial ATP synthase, is observed in most prevalent human carcinomas favoring metabolic rewiring to an enhanced glycolysis and cancer progression. Consistently, a high expression of IF1 in hepatocarcinomas and in carcinomas of the lung, bladder, and stomach and in gliomas is a biomarker of bad patient prognosis. In contrast to these findings, we have previously reported that a high expression level of IF1 in breast carcinomas is indicative of less chance to develop metastatic disease. This finding is especially relevant in the bad prognosis group of patients bearing triple-negative breast carcinomas. To investigate the molecular mechanisms that underlie the differential behavior of IF1 in breast cancer progression, we have developed the triple-negative BT549 breast cancer cell line that overexpresses IF1 stably. When compared to controls, IF1-cells partially shut down respiration and enhance aerobic glycolysis. Transcriptomic analysis suggested that migration and invasion were specifically inhibited in IF1-overexpressing breast cancer cells. Analysis of gene expression by qPCR and western blotting indicate that IF1 overexpression supports the maintenance of components of the extracellular matrix (ECM) and E-cadherin concurrently with the downregulation of components and signaling pathways involved in epithelial to mesenchymal transition. The overexpression of IF1 in breast cancer cells has no effect in the rates of cellular proliferation and in the cell death response to staurosporine and hydrogen peroxide. However, the overexpression of IF1 significantly diminishes the ability of the cells to grow in soft agar and to migrate and invade when compared to control cells. Overall, the results indicate that IF1 overexpression despite favoring a metabolic phenotype prone to cancer progression in the specific case of breast cancer cells also promotes the maintenance of the ECM impeding metastatic disease. These findings hence provide a mechanistic explanation to the better prognosis of breast cancer patients bearing tumors with high expression level of IF1.CN-T and IM-R were supported by pre-doctoral FPI-MEC and JAE-CSIC fellowships, respectively. This work was supported by grants from the Ministerio de Economía y Competitividad (SAF2013-41945-R; SAF2016-75916-R), Comunidad Madrid (S2011/BMD-2402), and Fundación Ramón Areces 2015, Spain.Peer reviewedPeer Reviewe

Oxidative stress influence on renal dysfunction in patients with obstructive jaundice: A case and control prospective study

Obstructive Jaundice (OJ) is associated with a significant risk of developing acute renal failure (ARF). The involvement of oxidative stress in the development of cholestasis has been demonstrated in different experimental models. However, its role in the morbidity of human cholestasis is far to be elucidated. The aim of the study was the evaluation of oxidative stress markers in blood from patients with OJ and its relation to complications and benign/malignant evolution of cholestasis. Methods: A prospective cross-sectional study of 105 patients with OJ and 34 control subjects were included. Several markers of liver function and oxidative stress, such as lipoperoxides (LPO), as well as reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. Results: The patients with OJ showed a marked increase in plasma levels of LPO, SOD and GSH, while GSH-Px levels were decreased. The increase in lipid peroxidation products and the depletion of SOD activity in blood were also related to renal dysfunction. The highest level of LPO was associated with malignant etiology of the disease. The logistic regression analysis showed that the age of the patient and the levels of LPO in blood were predictors of renal dysfunction in OJ patients. Conclusions: This study demonstrates a correlation between oxidative stress and renal dysfunction patients with OJ.Instituto de Salud Carlos III PI02/015

Unusual Vermamoeba Vermiformis Strain Isolated from Snow in Mount Teide, Tenerife, Canary Islands, Spain

Background: Free-living amoebae (FLA) are protozoa that are widely distributed in the environment mainly in water and soil related habitats. Thermophilic amoebae are among the most common FLA in water bodies, being Vermamoeba vermiformis one of the most common species reported worldwide from these sources. Interestingly, V. vermiformis has often been reported to survive at high temperatures and osmotic pressure worldwide.Materials and Methods: In this study, snow samples were collected from Mount Teide, Tenerife, Canary Islands during the winter season of 2014. The samples were culture on non nutrient agar plates and checked daily for the presence of FLA. After a week, V. vermiformis amoebae were observed in the plates incubated at room temperature and 37ºC.Results: Molecular characterization was carried out by amplifying the 18S rDNA gene and DNA sequencing, confirmed that the isolated strain belonged to Vermamoeba vermiformis species.Conclusion: To the best of our knowledge, this is the first report of Vermamoeba vermiformis isolation from such an inusual habitat (low temperatures and high altitude) and the first report of these species in the Canary islands