Defects in cytochrome oxidase assembly in humans: lessons from yeastThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

2006 ◽  
Vol 84 (6) ◽  
pp. 859-869 ◽  
Author(s):  
Jennifer M. Zee ◽  
D. Moira Glerum

The biogenesis of the inner mitochondrial membrane enzyme cytochrome c oxidase (COX) is a complex process that requires the actions of ancillary proteins, collectively called assembly factors. Studies with the yeast Saccharomyces cerevisiae have provided considerable insight into the COX assembly pathway and have proven to be a fruitful model for understanding the molecular bases for inherited COX deficiencies in humans. In this review, we focus on critical steps in the COX assembly pathway. These processes are conserved from yeast to humans and are known to be involved in the etiology of human COX deficiencies. The contributions from our studies in yeast suggest that this organism remains an excellent model system for delineating the molecular mechanisms underlying COX assembly defects in humans. Current progress suggests that a complete picture of COX assembly will be achieved in the near future.


2011 ◽  
Vol 10 (10) ◽  
pp. 1367-1369 ◽  
Author(s):  
Shigeyuki Kawai ◽  
Jörg Urban ◽  
Manuele Piccolis ◽  
Nicolas Panchaud ◽  
Claudio De Virgilio ◽  
...  

ABSTRACTTORC1-dependent phosphorylation ofSaccharomyces cerevisiaeSch9 was dramatically reduced upon exposure to a protonophore or in respiration-incompetent ρ0cells but not in respiration-incompetentpetmutants, providing important insight into the molecular mechanisms governing interorganellar signaling in general and retrograde signaling in particular.



Author(s):  
Joann Diray-Arce ◽  
Maria-Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  

Approaches to identification of metabolites have progressed from early biochemical pathway evaluation to modern high dimensional metabolomics which is a powerful tool to identify and characterize biomarkers of health and disease. While traditionally considered relevant in the context of classic metabolic diseases, immunometabolism has emerged as an important area of study as leukocytes generate key metabolites important to innate and adaptive immunity. Herein we discuss the metabolomic signatures and pathways perturbed during infection as well as vaccination. For example, changes in lipid and amino acid pathways (e.g., tryptophan, serine, and threonine) have been noted during infection while carbohydrate and bile acid pathways have shift upon vaccination. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying host response to infection and vaccination, and its integration with other systems biology platforms will add further impact to our studies of health and disease.



2019 ◽  
Vol 20 (15) ◽  
pp. 3673 ◽  
Author(s):  
Lismont ◽  
Revenco ◽  
Fransen

Hydrogen peroxide (H2O2), a non-radical reactive oxygen species generated during many (patho)physiological conditions, is currently universally recognized as an important mediator of redox-regulated processes. Depending on its spatiotemporal accumulation profile, this molecule may act as a signaling messenger or cause oxidative damage. The focus of this review is to comprehensively evaluate the evidence that peroxisomes, organelles best known for their role in cellular lipid metabolism, also serve as hubs in the H2O2 signaling network. We first briefly introduce the basic concepts of how H2O2 can drive cellular signaling events. Next, we outline the peroxisomal enzyme systems involved in H2O2 metabolism in mammals and reflect on how this oxidant can permeate across the organellar membrane. In addition, we provide an up-to-date overview of molecular targets and biological processes that can be affected by changes in peroxisomal H2O2 metabolism. Where possible, emphasis is placed on the molecular mechanisms and factors involved. From the data presented, it is clear that there are still numerous gaps in our knowledge. Therefore, gaining more insight into how peroxisomes are integrated in the cellular H2O2 signaling network is of key importance to unravel the precise role of peroxisomal H2O2 production and scavenging in normal and pathological conditions.



Metabolites ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 492
Author(s):  
Joann Diray-Arce ◽  
Maria Giulia Conti ◽  
Boryana Petrova ◽  
Naama Kanarek ◽  
Asimenia Angelidou ◽  
...  

Approaches to the identification of metabolites have progressed from early biochemical pathway evaluation to modern high-dimensional metabolomics, a powerful tool to identify and characterize biomarkers of health and disease. In addition to its relevance to classic metabolic diseases, metabolomics has been key to the emergence of immunometabolism, an important area of study, as leukocytes generate and are impacted by key metabolites important to innate and adaptive immunity. Herein, we discuss the metabolomic signatures and pathways perturbed by the activation of the human immune system during infection and vaccination. For example, infection induces changes in lipid (e.g., free fatty acids, sphingolipids, and lysophosphatidylcholines) and amino acid pathways (e.g., tryptophan, serine, and threonine), while vaccination can trigger changes in carbohydrate and bile acid pathways. Amino acid, carbohydrate, lipid, and nucleotide metabolism is relevant to immunity and is perturbed by both infections and vaccinations. Metabolomics holds substantial promise to provide fresh insight into the molecular mechanisms underlying the host immune response. Its integration with other systems biology platforms will enhance studies of human health and disease.



Author(s):  
Valentina Lodde ◽  
Silvia C. Modina ◽  
Alberto M. Luciano

In her comment entitled ‘Nuclear histochemistry: its history in fifty volumes’ (Eur J Histochem 2006; 50:79-81) Maria Gabriella Manfredi Romanini referred to “nuclear histochemistry” as a “real molecular biology in situ, applied to research on dynamic processes in the nucleus, which makes the microscopic and histochemical approach absolutely irreplaceable for the progress of our understanding of cell biology”. These words perfectly exemplify the research path that is elucidating the process of remodeling of chromatin configuration within the nucleus of the mammalian oocyte. This process, which occurs towards the end of the oocyte differentiation phase before meiotic resumption, has received much attention in the last decade since it has a tremendous impact on the capability of the oocyte to generate an embryo after fertilization. The study of the oocyte chromatin by means of classical morphological and histochemical approaches has given a fundamental contribution to our understanding of oocyte biology and has paved the way to functional and mechanistic studies. Several research groups worldwide, including ours, are indeed dedicating a large amount of studies to find the relationship between morphological and functional aspects of the oocyte chromatin remodeling process, to reveal the molecular mechanisms involved, as well as to clarify the contribution of the follicular compartment. Here, we summarize some studies intended to give insight into the mechanism( s) regulating this complex process, including recent findings indicating that ovarian granulosa cells and their coupling with the oocyte through gap junctions are implicated in such a process.



2016 ◽  
Vol 2 (2) ◽  
pp. 93-110 ◽  
Author(s):  
Liezel Alsemgeest ◽  
Kobus Schoeman ◽  
Theo Swart

Imminent retirement: Pastors’ experience of their congregation, personal well-being and financesThe provisions of pastors to congregations is of great importance to the Dutch Reformed Church and its congregation. To retire is a complex process of transition affecting various aspects – among others psychological, spiritual and financial aspects. According to current estimates, more than half of the full-time pastors in the Dutch Reformed Church could retire within the next fifteen years. A quantitative online survey was conducted amongst pastors who will retire in the near future, their experience of their congregation, personal well-being and financial prospects before and during retirement was taken into account. For the first time research provides insight into what will happen in churches when a pastor retires. The information should provide valid conclusions and recommendations can be made regarding the demand for pastors (and students?) in order to plan for effective ministry within churches.



2019 ◽  
Vol 20 (24) ◽  
pp. 6166 ◽  
Author(s):  
Chenfei Zheng ◽  
Meixia Ye ◽  
Mengmeng Sang ◽  
Rongling Wu

Vegetative phase changes in plants describes the transition between juvenile and adult phases of vegetative growth before flowering. It is one of the most fundamental mechanisms for plants to sense developmental signals, presenting a complex process involving many still-unknown determinants. Several studies in annual and perennial plants have identified the conservative roles of miR156 and its targets, SBP/SPL genes, in guiding the switch of plant growth from juvenile to adult phases. Here, we review recent progress in understanding the regulation of miR156 expression and how miR156-SPLs mediated plant age affect other processes in Arabidopsis. Powerful high-throughput sequencing techniques have provided rich data to systematically study the regulatory mechanisms of miR156 regulation network. From this data, we draw an expanded miR156-regulated network that links plant developmental transition and other fundamental biological processes, gaining novel and broad insight into the molecular mechanisms of plant-age-related processes in Arabidopsis.



2007 ◽  
Vol 148 (15) ◽  
pp. 697-702 ◽  
Author(s):  
Marianna Murányi ◽  
Zsombor Lacza

It is now known that astrocytes are not merely supporting cells but they also play an important role in neuronal funcions. Astrocytes tightly ensheat neuronal synapses and regulate the excitation of neurons by uptaking neurotransmitters; reglulate the cerebral blood flow, cerebral fluid volume and extracellular concentrations of ions. They also supply fuel in the form of lactate and provide free radical scavangers such as glutathione for active neurons. These facts indicate that impaired function of astrocytes may lead to neuronal dysfunction. After brain injury (stroke, trauma or tumors) astrocytes are swollen and release active molecules such as glutamate or free radicals resulting in neuronal dysfunction. Thus, investigation of the molecular mechanisms of astrocyte function may reveal novel targets for the development of therapeutic tools in neuronal diseases.



2012 ◽  
Vol 11 (1) ◽  
pp. 25-32 ◽  
Author(s):  
James West ◽  
James E. Loyd ◽  
Rizwan Hamid

For more than 60 years, researchers have sought to understand the molecular basis of idiopathic pulmonary arterial hypertension (PAH). Recognition of the heritable form of the disease led to the creation of patient registries in the 1980s and 1990s, and discovery of BMPR2 as the cause of roughly 80% of heritable PAH in 2000. With discovery of the disease gene came opportunity for intervention, with focus on 2 alternative approaches. First, it may be possible to correct the effects of BMPR2 mutation directly through interventions targeted at correction of trafficking defects, increasing expression of the unmutated allele, and correction of splicing defects. Second, therapeutic interventions are being targeted at the signaling consequences of BMPR2 mutation. In particular, therapies targeting cytoskeletal and metabolic defects caused by BMPR2 mutation are currently in trials, or will be ready for human trials in the near future. Translation of these findings into therapies is the culmination of decades of research, and holds great promise for treatment of the underlying molecular bases of disease.



2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.



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