Amino Acid Catabolism in Plants Hildebrandt, Tatjana M; Nunes Nesi, Adriano; Araújo, Wagner L ...
Molecular plant,
11/2015, Letnik:
8, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Amino acids have various prominent functions in plants. Besides their usage during protein biosynthesis, they also represent building blocks for several other biosynthesis pathways and play pivotal ...roles during signaling processes as well as in plant stress response. In general, pool sizes of the 20 amino acids differ strongly and change dynamically depending on the developmental and physiological state of the plant cell. Besides amino acid biosynthesis, which has already been investigated in great detail, the catabolism of amino acids is of central importance for adjusting their pool sizes but so far has drawn much less attention. The degradation of amino acids can also contribute substantially to the energy state of plant cells under certain physiological conditions, e.g. carbon starvation. In this review, we discuss the biological role of amino acid catabolism and summarize current knowledge on amino acid degradation pathways and their regulation in the context of plant cell physiology.
The long-term prognosis for clear cell renal cell carcinoma (ccRCC) is dramatically altered by the development of metastatic recurrence. However, there are very few indicators that can predict which ...patient will develop a recurrence. MicroRNAs regulate many cellular processes and have been shown to be associated with cancer development and recurrence. More recently it has been shown that microRNA genes can be epigenetically modified in cancer, resulting in aberrant silencing of microRNA genes with tumor suppressor functions. In this study, we show that two genes encoding for hsa-miR-9 are significantly hypermethylated in ccRCC tumors compared with adjacent normal tissues (P-value <0.001 for both miR-9-1 and miR-9-3) resulting in decreased expression, and that the methylation of these genes was more significant in DNA obtained from the primary tumor for patients who developed a recurrence (P-value: 0.012 and 0.009 for miR-9-1 and miR-9-3, respectively) than in tumors from nonrecurrent patients. Furthermore, methylation of miR-9-3 was significantly associated with an increased risk of recurrence (hazard ratio: 5.85, 95% confidence intervals: 1.30-26.35) and high methylation levels of either miR-9-1 or miR-9-3 resulted in a significant, nearly 30-month decrease in recurrence-free survival time (P-value: 0.034 and 0.007 for miR-9-1 and miR-9-3, respectively). Our results demonstrate that hsa-miR-9 is involved in the development of ccRCC while also having a role in the development of metastatic recurrence.
Background & AimATMPs are medicinal products based on gene therapy, somatic cell therapy or tissue engineering. Regulation (EU) 1394/2007 has been designed to ensure the free movement of ATMPs within ...the EU to facilitate their access to the EU market and to foster the competitiveness of European pharmaceutical companies while guaranteeing the highest level of health protection for patients.As ATMPs pose specific challenges to developers, manufacturers, regulators and clinicians in terms of complexity and risk profile, distinct rules have been developed for the manufacture and clinical testing of ATMPs. Article 4 of Regulation 1394/2007 has required the European Commission to establish GCP guidelines specific to ATMPs. The stakeholder consultation performed for this purpose, however, has not addressed the qualification of clinical trial sites and investigators. It remains to be elucidated how clinical trial sites and investigators using ATMPs can give documented evidence of their specific qualification, and how Ethics Committees can draw on expertise needed to assess this special group of innovative medicines.Methods, Results & ConclusionChimeric antigen receptor (CAR)-transduced cells highlight the challenges in qualification of trial sites and investigators. With patients in desperate need, clinicians have put growing pressure on regulators and politicians to render these promising therapies more rapidly available, irrespective of existing gaps in infrastructure, clinical expertise and concepts for the coverage of costs.From the standpoint of an Ethics Committee, documented evidence of the qualification of trial sites and investigators using CAR-T cells and similar ATMPs should include- a risk-benefit analysis that addresses the characteristics of the respective ATMP specifically and appropriately,- the capacity to monitor, grade, manage and document the acute toxicity inherent in this approach,- the infrastructure needed to handle these toxicities,- a data registry and repository for adverse events related to the use of ATMPs in humans,- a recognizable network of collaborating centers who exchange knowledge, share training and help each other in this challenging and important field.Ethics committees will depend on independent experts in ATMPs, especially high-risk (and high-demand) products, to provide guidance in assessing clinical centers and investigators as qualified for these special medicines. Consensus statements by professional societies would be highly welcome.
Plant responses to abiotic stress include various modifications in amino acid metabolism. By using a hydroponic culture system, we systematically investigate modification in amino acid profiles and ...the proteome of Arabidopsis thaliana leaves during initial recovery from low water potential or high salinity. Both treatments elicited oxidative stress leading to a biphasic stress response during recovery. Degradation of highly abundant proteins such as subunits of photosystems and ribosomes contributed to an accumulation of free amino acids. Catabolic pathways for several low abundant amino acids were induced indicating their usage as an alternative respiratory substrate to compensate for the decreased photosynthesis. Our results demonstrate that rapid detoxification of potentially detrimental amino acids such as Lys is a priority during the initial stress recovery period. The content of Pro, which acts as a compatible osmolyte during stress, was adjusted by balancing its synthesis and catabolism both of which were induced both during and after stress treatments. The production of amino acid derived secondary metabolites was up‐regulated specifically during the recovery period, and our dataset also indicates increased synthesis rates of the precursor amino acids. Overall, our results support a tight relationship between amino acid metabolism and stress responses.
Plant amino acid metabolism strongly reacts to different abiotic stress conditions. This study addresses metabolic events during the recovery phase from low water potential or high salinity in Arabidopsis thaliana. The main effects were an induction of the synthesis pathways for amino acids that function as either nitrogen stores or precursors for secondary metabolites and increased catabolism of proline as well as low abundant amino acids.
Hydrogen sulfide is a potent toxin of aerobic respiration, but also has physiological functions as a signalling molecule and as a substrate for ATP production. A mitochondrial pathway catalyzing ...sulfide oxidation to thiosulfate in three consecutive reactions has been identified in rat liver as well as in the body-wall tissue of the lugworm, Arenicola marina. A membrane-bound sulfide : quinone oxidoreductase converts sulfide to persulfides and transfers the electrons to the ubiquinone pool. Subsequently, a putative sulfur dioxygenase in the mitochondrial matrix oxidizes one persulfide molecule to sulfite, consuming molecular oxygen. The final reaction is catalyzed by a sulfur transferase, which adds a second persulfide from the sulfide : quinone oxidoreductase to sulfite, resulting in the final product thiosulfate. This role in sulfide oxidation is an additional physiological function of the mitochondrial sulfur transferase, rhodanese.
Key message
During abiotic stress low abundant amino acids are not synthesized but they accumulate due to increased protein turnover under conditions inducing carbohydrate starvation (dehydration, ...salt stress, darkness) and are degraded.
Metabolic adaptation is crucial for abiotic stress resistance in plants, and accumulation of specific amino acids as well as secondary metabolites derived from amino acid metabolism has been implicated in increased tolerance to adverse environmental conditions. The role of proline, which is synthesized during Arabidopsis stress response to act as a compatible osmolyte, has been well established. However, conclusions drawn about potential functions of other amino acids such as leucine, valine, and isoleucine are not entirely consistent. This study reevaluates published datasets with a special emphasis on changes in the free amino acid pool and transcriptional regulation of the associated anabolic and catabolic pathways. In order to gain a comprehensive overview about the general direction of amino acid metabolism under abiotic stress conditions a complete map of all currently known enzymatic steps involved in amino acid synthesis and degradation was assembled including also the initial steps leading to the synthesis of secondary metabolites. Microarray datasets and amino acid profiles of Arabidopsis plants exposed to dehydration, high salinity, extended darkness, cold, and heat were systematically analyzed to identify trends in fluxes of amino acid metabolism. Some high abundant amino acids such as proline, arginine, asparagine, glutamine, and GABA are synthesized during abiotic stress to act as compatible osmolytes, precursors for secondary metabolites, or storage forms of organic nitrogen. In contrast, most of the low abundant amino acids are not synthesized but they accumulate due to increased protein turnover under conditions inducing carbohydrate starvation (dehydration, salt stress, extended darkness) and are degraded.
Summary
Mitochondria host vital cellular functions, including oxidative phosphorylation and co‐factor biosynthesis, which are reflected in their proteome. At the cellular level plant mitochondria are ...organized into hundreds of discrete functional entities, which undergo dynamic fission and fusion. It is the individual organelle that operates in the living cell, yet biochemical and physiological assessments have exclusively focused on the characteristics of large populations of mitochondria. Here, we explore the protein composition of an individual average plant mitochondrion to deduce principles of functional and structural organisation. We perform proteomics on purified mitochondria from cultured heterotrophic Arabidopsis cells with intensity‐based absolute quantification and scale the dataset to the single organelle based on criteria that are justified by experimental evidence and theoretical considerations. We estimate that a total of 1.4 million protein molecules make up a single Arabidopsis mitochondrion on average. Copy numbers of the individual proteins span five orders of magnitude, ranging from >40 000 for Voltage‐Dependent Anion Channel 1 to sub‐stoichiometric copy numbers, i.e. less than a single copy per single mitochondrion, for several pentatricopeptide repeat proteins that modify mitochondrial transcripts. For our analysis, we consider the physical and chemical constraints of the single organelle and discuss prominent features of mitochondrial architecture, protein biogenesis, oxidative phosphorylation, metabolism, antioxidant defence, genome maintenance, gene expression, and dynamics. While assessing the limitations of our considerations, we exemplify how our understanding of biochemical function and structural organization of plant mitochondria can be connected in order to obtain global and specific insights into how organelles work.
Significance Statement
We explore the structure and function of a single plant mitochondrion by scaling down a quantitative proteomic dataset of Arabidopsis cell culture mitochondria to calculate the copy numbers of individual protein species for a single organelle.
Several commercial and academic autologous chimeric antigen receptor T-cell (CAR-T) products targeting CD19 have been approved in Europe for relapsed/refractory B-cell acute lymphoblastic leukemia, ...high-grade B-cell lymphoma and mantle cell lymphoma. Products for other diseases such as multiple myeloma and follicular lymphoma are likely to be approved by the European Medicines Agency in the near future.
The European Society for Blood and Marrow Transplantation (EBMT)-Joint Accreditation Committee of ISCT and EBMT (JACIE) and the European Haematology Association collaborated to draft best practice recommendations based on the current literature to support health care professionals in delivering consistent, high-quality care in this rapidly moving field.
Thirty-six CAR-T experts (medical, nursing, pharmacy/laboratory) assembled to draft recommendations to cover all aspects of CAR-T patient care and supply chain management, from patient selection to long-term follow-up, post-authorisation safety surveillance and regulatory issues.
We provide practical, clinically relevant recommendations on the use of these high-cost, logistically complex therapies for haematologists/oncologists, nurses and other stakeholders including pharmacists and health sector administrators involved in the delivery of CAR-T in the clinic.
The design of the MEG II experiment Baldini, A. M; Baracchini, E; Bemporad, C ...
The European physical journal. C, Particles and fields,
05/2018, Letnik:
78, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The MEG experiment, designed to search for the Formula omitted decay, completed data-taking in 2013 reaching a sensitivity level of Formula omitted for the branching ratio. In order to increase the ...sensitivity reach of the experiment by an order of magnitude to the level of Formula omitted, a total upgrade, involving substantial changes to the experiment, has been undertaken, known as MEG II. We present both the motivation for the upgrade and a detailed overview of the design of the experiment and of the expected detector performance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plants use amino acids as respiratory substrates during stress-induced energy shortage, which is regulated by TOR and SnRK1 signaling. Cysteine triggers abscisic acid production and stomatal closure ...during drought stress.
Abstract
The adaptation of plant metabolism to stress-induced energy deficiency involves profound changes in amino acid metabolism. Anabolic reactions are suppressed, whereas respiratory pathways that use amino acids as alternative substrates are activated. This review highlights recent progress in unraveling the stress-induced amino acid oxidation pathways, their regulation, and the role of amino acids as signaling molecules. We present an updated map of the degradation pathways for lysine and the branched-chain amino acids. The regulation of amino acid metabolism during energy deprivation, including the coordinated induction of several catabolic pathways, is mediated by the balance between TOR and SnRK signaling. Recent findings indicate that some amino acids might act as nutrient signals in TOR activation and thus promote a shift from catabolic to anabolic pathways. The metabolism of the sulfur-containing amino acid cysteine is highly interconnected with TOR and SnRK signaling. Mechanistic details have recently been elucidated for cysteine signaling during the abscisic acid-dependent drought response. Local cysteine synthesis triggers abscisic acid production and, in addition, cysteine degradation produces the gaseous messenger hydrogen sulfide, which promotes stomatal closure via protein persulfidation. Amino acid signaling in plants is still an emerging topic with potential for fundamental discoveries.
PDF
