Reciprocal influence of the p53 and the hypoxic pathways

When cells sense a decrease in oxygen availability (hypoxia), they develop adaptive responses in order to sustain this condition and survive. If hypoxia lasts too long or is too severe, the cells eventually die. Hypoxia is also known to modulate the p53 pathway, in a manner dependent or not of HIF-1 (hypoxia-inducible factor-1), the main transcription factor activated by hypoxia. The p53 protein is a transcription factor, which is rapidly stabilised by cellular stresses and which has a major role in the cell responses to these stresses. The aim of this review is to compile what has been reported until now about the interconnection between these two important pathways. Indeed, according to the cell line, the severity and the duration of hypoxia, oxygen deficiency influences very differently p53 protein level and activity. Conversely, p53 is also described to affect HIF-1α stability, one of the two subunits of HIF-1, and HIF-1 activity. The direct and indirect interactions between HIF-1α and p53 are described as well as the involvement in this complex network of their respective ubiquitin ligases von Hippel Lindau protein and murine double minute 2. Finally, the synergistic or antagonistic effects of p53 and HIF-1 on some important cellular pathways are discussed

How Do Human Cells React to the Absence of Mitochondrial DNA?

Mitochondrial biogenesis is under the control of two different genetic systems: the nuclear genome (nDNA) and the mitochondrial genome (mtDNA). The mtDNA is a circular genome of 16.6 kb encoding 13 of the approximately 90 subunits that form the respiratory chain, the remaining ones being encoded by the nDNA. Eukaryotic cells are able to monitor and respond to changes in mitochondrial function through alterations in nuclear gene expression, a phenomenon first defined in yeast and known as retrograde regulation. To investigate how the cellular transcriptome is modified in response to the absence of mtDNA, we used Affymetrix HG-U133A GeneChip arrays to study the gene expression profile of two human cell lines, 143BTK(-) and A549, which had been entirely depleted of mtDNA (rho(o) cells), and compared it with that of corresponding undepleted parental cells (rho(+) cells).Our data indicate that absence of mtDNA is associated with: i) a down-regulation of cell cycle control genes and a reduction of cell replication rate, ii) a down-regulation of nuclear-encoded subunits of complex III of the respiratory chain and iii) a down-regulation of a gene described as the human homolog of ELAC2 of E. coli, which encodes a protein that we show to also target to the mitochondrial compartment.Our results indicate a strong correlation between mitochondrial biogenesis and cell cycle control and suggest that some proteins could have a double role: for instance in controlling both cell cycle progression and mitochondrial functions. In addition, the finding that ELAC2 and maybe other transcripts that are located into mitochondria, are down-regulated in rho(o) cells, make them good candidates for human disorders associated with defective replication and expression of mtDNA

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Assessment of emission reduction potential of Mumbai metro rail

First line of Mumbai metro rail system was implemented in 2014 for reduction in traffic congestion and to provide a better connectivity between eastern and western suburbs of Mumbai metropolitan region (MMR). Apart from connectivity, reduction in greenhouse gases (GHG), gaseous pollutants like carbon monoxide (CO), hydrocarbon (HC), oxides of nitrogen (NOx), particulate matter (PM) were the main goal behind implementation of metro. In this study, we analyse the reduction in carbon dioxide (CO2) and other emissions due to shift of commuters to metro from other mode of transportation. In addition, monetary savings in travel time is also determined as travel time is the main attraction for using metro. The emissions were estimated through modal shift of passengers by converting the ridership data to equivalent number of vehicles on road. Our analysis shows modal shift resulted in reduction of 22.7 tonne of CO2 emission per day but similar to 75.6 tonne of CO2 is emitted per day from the electricity consumed in metro operation. However, pollutants like CO, HC were reduced by metro and high savings in value of travel time was obtained. Overall, the results illustrate that so far the metro rail is yet to achieve reduction in greenhouse gases (GHG) emissions since a major shift occurred from public transportation. However, with increase in ridership metro rail can achieve the benefits in reduction of emissions. (C) 2018 Elsevier Ltd. All rights reserved

Life cycle assessment of potential municipal solid waste management strategies for Mumbai, India

Dumping of municipal solid waste into uncontrolled dumpsites is the most common method of waste disposal in most cities of India. These dumpsites are posing a serious challenge to environmental quality and sustainable development. Mumbai, which generates over 9000t of municipal solid waste daily, also disposes of most of its waste in open dumps. It is important to analyse the impact of municipal solid waste disposal today and what would be the impact under integrated waste management schemes. In this study, life cycle assessment methodology was used to determine the impact of municipal solid waste management under different scenarios. Six different scenarios were developed as alternatives to the current practice of open dumping and partially bioreactor landfilling. The scenarios include landfill with biogas collection, incineration and different combinations of recycling, landfill, composting, anaerobic digestion and incineration. Global warming, acidification, eutrophication and human toxicity were assessed as environmental impact categories. The sensitivity analysis shows that if the recycling rate is increased from 10% to 90%, the environmental impacts as compared with present scenario would reduce from 998.43kgCO(2) eqt(-1) of municipal solid waste, 0.124kgSO(2) eqt(-1), 0.46kgPO(4)(-3) eqt(-1), 0.44kg 1,4-DB eqt(-1) to 892.34kgCO(2) eqt(-1), 0.121kgSO(2) eqt(-1), 0.36kgPO(4)(-3) eqt(-1), 0.40kg 1,4-DB eqt(-1), respectively. An integrated municipal solid waste management approach with a mix of recycling, composting, anaerobic digestion and landfill had the lowest overall environmental impact. The technologies, such as incineration, would reduce the global warming emission because of the highest avoided emissions, however, human toxicity would increase

Effect of catch bonding on transport of cellular cargo by dynein motors

Recent experiments have demonstrated that dynein motors exhibit catch bonding behavior, in which the unbinding rate of a single dynein decreases with increasing force, for a certain range of force. Motivated by these experiments, we study the effect of catch bonding on unidirectional transport properties of cellular cargo carried by multiple dynein motors. We introduce a threshold force bond deformation (TFBD) model, consistent with the experiments, wherein catch bonding sets in beyond a critical applied load force. We find catch bonding can result in dramatic changes in the transport properties, which are in sharp contrast to kinesin-driven unidirectional transport, where catch bonding is absent. We predict that under certain conditions, the average velocity of the cellular cargo can actually increase as applied load is increased. We characterize the transport properties in terms of a velocity profile plot in the parameter space of the catch bond strength and the stall force of the motor. This plot yields predictions that may be experimentally accessed by suitable modifications of motor transport and binding properties