SUMMARY
Nitrate (NO3−) and phosphate (Pi) deficiencies are the major constraints for chickpea productivity, significantly impacting global food security. However, excessive fertilization is expensive ...and can also lead to environmental pollution. Therefore, there is an urgent need to develop chickpea cultivars that are able to grow on soils deficient in both NO3− and Pi. This study focused on the identification of key NO3− and/or Pi starvation‐responsive metabolic pathways in the leaves and roots of chickpea grown under single and double nutrient deficiencies of NO3− and Pi, in comparison with nutrient‐sufficient conditions. A global metabolite analysis revealed organ‐specific differences in the metabolic adaptation to nutrient deficiencies. Moreover, we found stronger adaptive responses in the roots and leaves to any single than combined nutrient‐deficient stresses. For example, chickpea enhanced the allocation of carbon among nitrogen‐rich amino acids (AAs) and increased the production of organic acids in roots under NO3− deficiency, whereas this adaptive response was not found under double nutrient deficiency. Nitrogen remobilization through the transport of AAs from leaves to roots was greater under NO3− deficiency than double nutrient deficiency conditions. Glucose‐6‐phosphate and fructose‐6‐phosphate accumulated in the roots under single nutrient deficiencies, but not under double nutrient deficiency, and higher glycolytic pathway activities were observed in both roots and leaves under single nutrient deficiency than double nutrient deficiency. Hence, the simultaneous deficiency generated a unique profile of metabolic changes that could not be simply described as the result of the combined deficiencies of the two nutrients.
Significance Statement
There is no available information on the adaptive mechanisms, in terms of metabolic changes, which enable plants to respond to double nutrient nitrate (NO3−) and phosphate (Pi) starvation. The results of this study allow us to understand and discover promising key metabolic pathways responsive to single and/or double NO3− and Pi starvation in chickpea plants, which can be targeted for genetic engineering to develop chickpea cultivars that are more productive in N‐ and/or Pi‐poor soils.
The negative effects of phosphate (Pi) and/or nitrate (NO3−) fertilizers on the environment have raised an urgent need to develop crop varieties with higher Pi and/or nitrogen use efficiencies for ...cultivation in low‐fertility soils. Achieving this goal depends upon research that focuses on the identification of genes involved in plant responses to Pi and/or NO3− starvation. Although plant responses to individual deficiency in either Pi (–Pi/+NO3−) or NO3− (+Pi/–NO3−) have been separately studied, our understanding of plant responses to combined Pi and NO3− deficiency (–Pi/–NO3−) is still very limited. Using RNA‐sequencing approach, transcriptome changes in the roots and leaves of chickpea cultivated under –Pi/+NO3−, +Pi/–NO3− or –Pi/–NO3− conditions were investigated in a comparative manner. –Pi/–NO3− treatment displayed lesser effect on expression changes of genes related to Pi or NO3− transport, signalling networks, lipid remodelling, nitrogen and Pi scavenging/remobilization/recycling, carbon metabolism and hormone metabolism than –Pi/+NO3− or +Pi/–NO3− treatments. Therefore, the plant response to –Pi/–NO3− is not simply an additive result of plant responses to –Pi/+NO3− and +Pi/–NO3− treatments. Our results indicate that nutrient imbalance is a stronger stimulus for molecular reprogramming than an overall deficiency.
Comparative transcriptome analyses revealed that combined phosphate (Pi) and nitrate (NO3−) deficiency had lower effects on expression changes of many Pi starvation‐responsive genes and NO3− starvation‐responsive genes than individual Pi and NO3− deficiencies did in chickpea plants.
The long road to leptin Friedman, Jeffrey
The Journal of clinical investigation,
12/2016, Volume:
126, Issue:
12
Journal Article
Peer reviewed
Open access
Leptin is an adipose tissue hormone that functions as an afferent signal in a negative feedback loop that maintains homeostatic control of adipose tissue mass. This endocrine system thus serves a ...critical evolutionary function by protecting individuals from the risks associated with being too thin (starvation) or too obese (predation and temperature dysregulation). Mutations in leptin or its receptor cause massive obesity in mice and humans, and leptin can effectively treat obesity in leptin-deficient patients. Leptin acts on neurons in the hypothalamus and elsewhere to elicit its effects, and mutations that affect the function of this neural circuit cause Mendelian forms of obesity. Leptin levels fall during starvation and elicit adaptive responses in many other physiologic systems, the net effect of which is to reduce energy expenditure. These effects include cessation of menstruation, insulin resistance, alterations of immune function, and neuroendocrine dysfunction, among others. Some or all of these effects are also seen in patients with constitutively low leptin levels, such as occur in lipodystrophy. Leptin is an approved treatment for generalized lipodystrophy, a condition associated with severe metabolic disease, and has also shown potential for the treatment of other types of diabetes. In addition, leptin restores reproductive capacity and increases bone mineral density in patients with hypothalamic amenorrhea, an infertility syndrome in females. Most obese patients have high endogenous levels of leptin, in some instances as a result of mutations in the neural circuit on which leptin acts, though in most cases, the pathogenesis of leptin resistance is not known. Obese patients with leptin resistance show a variable response to exogenous leptin but may respond to a combination of leptin plus amylin. Overall, the identification of leptin has provided a framework for studying the pathogenesis of obesity in the general population, clarified the nature of the biologic response to starvation, and helped to advance our understanding of the neural mechanisms that control feeding.
The appropriate measurement of food security is critical for targeting food and economic aid; supporting early famine warning and global monitoring systems; evaluating nutrition, health, and ...development programs; and informing government policy across many sectors. This important work is complicated by the multiple approaches and tools for assessing food security. In response, we have prepared a compendium and review of food security assessment tools in which we review issues of terminology, measurement, and validation. We begin by describing the evolving definition of food security and use this discussion to frame a review of the current landscape of measurement tools available for assessing food security. We critically assess the purpose/s of these tools, the domains of food security assessed by each, the conceptualizations of food security that underpin each metric, as well as the approaches that have been used to validate these metrics. Specifically, we describe measurement tools that 1) provide national-level estimates of food security, 2) inform global monitoring and early warning systems, 3) assess household food access and acquisition, and 4) measure food consumption and utilization. After describing a number of outstanding measurement challenges that might be addressed in future research, we conclude by offering suggestions to guide the selection of appropriate food security metrics.
Tree mortality rates appear to be increasing in moist tropical forests (MTFs) with significant carbon cycle consequences. Here, we review the state of knowledge regarding MTF tree mortality, create a ...conceptual framework with testable hypotheses regarding the drivers, mechanisms and interactions that may underlie increasing MTF mortality rates, and identify the next steps for improved understanding and reduced prediction. Increasing mortality rates are associated with rising temperature and vapor pressure deficit, liana abundance, drought, wind events, fire and, possibly, CO2 fertilization-induced increases in stand thinning or acceleration of trees reaching larger, more vulnerable heights. The majority of these mortality drivers may kill trees in part through carbon starvation and hydraulic failure. The relative importance of each driver is unknown. High species diversity may buffer MTFs against large-scale mortality events, but recent and expected trends in mortality drivers give reason for concern regarding increasing mortality within MTFs. Models of tropical tree mortality are advancing the representation of hydraulics, carbon and demography, but require more empirical knowledge regarding the most common drivers and their subsequent mechanisms. We outline critical datasets and model developments required to test hypotheses regarding the underlying causes of increasing MTF mortality rates, and improve prediction of future mortality under climate change.
Autophagy is a highly conserved process and is essential for the maintenance of cellular homeostasis. Autophagy occurs at a basal level in all cells, but it can be up-regulated during stress, ...starvation, or infection. Misregulation of autophagy has been linked to various disorders, including cancer, neurodegeneration, and immune diseases. Here, we discuss the essential proteins acting in the formation of an autophagosome, with a focus on the ULK and VPS34 kinase complexes, phosphatidylinositol 3-phosphate effector proteins, and the transmembrane autophagy-related protein ATG9. The function and regulation of these and other autophagy-related proteins acting during formation will be addressed, in particular during amino acid starvation.
The lysosomal-autophagic pathway is activated by starvation and plays an important role in both cellular clearance and lipid catabolism. However, the transcriptional regulation of this pathway in ...response to metabolic cues is uncharacterized. Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1α and Ppar1α. Thus, during starvation a transcriptional mechanism links the autophagic pathway to cellular energy metabolism. The conservation of this mechanism in Caenorhabditis elegans suggests a fundamental role for TFEB in the evolution of the adaptive response to food deprivation. Viral delivery of TFEB to the liver prevented weight gain and metabolic syndrome in both diet-induced and genetic mouse models of obesity, suggesting a new therapeutic strategy for disorders of lipid metabolism.
Endogenous HMGB1 regulates autophagy Tang, Daolin; Kang, Rui; Livesey, Kristen M ...
The Journal of cell biology,
09/2010, Volume:
190, Issue:
5
Journal Article
Peer reviewed
Open access
Autophagy clears long-lived proteins and dysfunctional organelles and generates substrates for adenosine triphosphate production during periods of starvation and other types of cellular stress. Here ...we show that high mobility group box 1 (HMGB1), a chromatin-associated nuclear protein and extracellular damage-associated molecular pattern molecule, is a critical regulator of autophagy. Stimuli that enhance reactive oxygen species promote cytosolic translocation of HMGB1 and thereby enhance autophagic flux. HMGB1 directly interacts with the autophagy protein Beclin1 displacing Bcl-2. Mutation of cysteine 106 (C106), but not the vicinal C23 and C45, of HMGB1 promotes cytosolic localization and sustained autophagy. Pharmacological inhibition of HMGB1 cytoplasmic translocation by agents such as ethyl pyruvate limits starvation-induced autophagy. Moreover, the intramolecular disulfide bridge (C23/45) of HMGB1 is required for binding to Beclin1 and sustaining autophagy. Thus, endogenous HMGB1 is a critical pro-autophagic protein that enhances cell survival and limits programmed apoptotic cell death.
Autophagy is a catabolic process whereby cytoplasmic components are degraded within lysosomes, allowing cells to maintain energy homeostasis during nutrient depletion. Several studies reported that ...the CDK inhibitor p27
promotes starvation-induced autophagy by an unknown mechanism. Here we find that p27 controls autophagy via an mTORC1-dependent mechanism in amino acid-deprived cells. During prolonged starvation, a fraction of p27 is recruited to lysosomes, where it interacts with LAMTOR1, a component of the Ragulator complex required for mTORC1 activation. Binding of p27 to LAMTOR1 prevents Ragulator assembly and mTORC1 activation, promoting autophagy. Conversely, p27
cells exhibit elevated mTORC1 signalling as well as impaired lysosomal activity and autophagy. This is associated with cytoplasmic sequestration of TFEB, preventing induction of the lysosomal genes required for lysosome function. LAMTOR1 silencing or mTOR inhibition restores autophagy and induces apoptosis in p27
cells. Together, these results reveal a direct coordinated regulation between the cell cycle and cell growth machineries.
PDF
