scholarly journals Autophagy plays a double-edged sword role in liver diseases

2021 ◽  
Author(s):  
Jing-chao Zhou ◽  
Jing-lin Wang ◽  
Hao-zhen Ren ◽  
Xiao-lei Shi
Keyword(s):  
Liver Diseases ◽  
Alcoholic Hepatitis ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Building Blocks ◽  
Cell Types ◽  
Evolutionarily Conserved ◽  
Constitutive Process ◽  
New Strategies

Abstract As a highly evolutionarily conserved process, autophagy can be found in all types of eukaryotic cells. Such a constitutive process maintains cellular homeostasis in a wide variety of cell types through the encapsulation of damaged proteins or organelles into double-membrane vesicles. Autophagy not only simply eliminates materials but also serves as a dynamic recycling system that produces new building blocks and energy for cellular renovation and homeostasis. Previous studies have primarily recognized the role of autophagy in the degradation of dysfunctional proteins and unwanted organelles. However, there are findings of autophagy in physiological and pathological processes. In hepatocytes, autophagy is not only essential for homeostatic functions but also implicated in some diseases, such as viral hepatitis, alcoholic hepatitis, and hepatic failure. In the present review, we summarized the molecular mechanisms of autophagy and its role in several liver diseases and put forward several new strategies for the treatment of liver disease.

scholarly journals Autophagy regulation by acetylation—implications for neurodegenerative diseases

2021 ◽  
Vol 53 (1) ◽  
pp. 30-41
Author(s):  
Sung Min Son ◽  
So Jung Park ◽  
Marian Fernandez-Estevez ◽  
David C. Rubinsztein
Keyword(s):  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Cell Types ◽  
Double Membrane ◽  
Physiological Processes ◽  
Evolutionarily Conserved ◽  
Development And Aging ◽  
Catabolic Process

AbstractPosttranslational modifications of proteins, such as acetylation, are essential for the regulation of diverse physiological processes, including metabolism, development and aging. Autophagy is an evolutionarily conserved catabolic process that involves the highly regulated sequestration of intracytoplasmic contents in double-membrane vesicles called autophagosomes, which are subsequently degraded after fusing with lysosomes. The roles and mechanisms of acetylation in autophagy control have emerged only in the last few years. In this review, we describe key molecular mechanisms by which previously identified acetyltransferases and deacetylases regulate autophagy. We highlight how p300 acetyltransferase controls mTORC1 activity to regulate autophagy under starvation and refeeding conditions in many cell types. Finally, we discuss how altered acetylation may impact various neurodegenerative diseases in which many of the causative proteins are autophagy substrates. These studies highlight some of the complexities that may need to be considered by anyone aiming to perturb acetylation under these conditions.

scholarly journals The roles and mechanisms of hypoxia in liver fibrosis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyao Cai ◽  
Min Hu ◽  
Zhiyang Chen ◽  
Zeng Ling
Keyword(s):  
Quality Of Life ◽  
Liver Fibrosis ◽  
Theoretical Basis ◽  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Clinical Intervention ◽  
Chronic Liver Injury ◽  
Key Factor

AbstractLiver fibrosis occurs in response to any etiology of chronic liver injury. Lack of appropriate clinical intervention will lead to liver cirrhosis or hepatocellular carcinoma (HCC), seriously affecting the quality of life of patients, but the current clinical treatments of liver fibrosis have not been developed yet. Recent studies have shown that hypoxia is a key factor promoting the progression of liver fibrosis. Hypoxia can cause liver fibrosis. Liver fibrosis can, in turn, profoundly further deepen the degree of hypoxia. Therefore, exploring the role of hypoxia in liver fibrosis will help to further understand the process of liver fibrosis, and provide the theoretical basis for its diagnosis and treatment, which is of great significance to avoid further deterioration of liver diseases and protect the life and health of patients. This review highlights the recent advances in cellular and molecular mechanisms of hypoxia in developments of liver fibrosis.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals Nckβ Adapter Controls Neuritogenesis by Maintaining the Cellular Paxillin Level

2007 ◽  
Vol 27 (17) ◽  
pp. 6001-6011 ◽  
Author(s):  
Shengxi Guan ◽  
Mei Chen ◽  
David Woodley ◽  
Wei Li
Keyword(s):  
Pc12 Cells ◽  
Cortical Neurons ◽  
State Level ◽  
Cell Types ◽  
Steady State Level ◽  
Down Regulation ◽  
Evolutionarily Conserved ◽  
Rat Cortical Neurons ◽  
Interfering Rna

ABSTRACT The SH2/SH3 adapter Nck has an evolutionarily conserved role in neurons, linking the cell surface signals to actin cytoskeleton-mediated responses. The mechanism, however, remains poorly understood. We have investigated the role of Nck/Nckα/Nck1 versus Grb4/Nckβ/Nck2 side-by-side in the process of mammalian neuritogenesis. Here we show that permanent genetic silencing of Nckβ, but not Nckα, completely blocked nerve growth factor-induced neurite outgrowth in PC12 cells and dramatically disrupted the axon and dendrite tree in primary rat cortical neurons. By screening for changes among the components reportedly present in complex with Nck, we found that the steady-state level of paxillin was significantly reduced in Nckβ knockdown, but not Nckα knockdown, neurons. Interestingly, Nckβ knockdown did not affect the paxillin level in glial cells and several other cell types of various tissue origins. Genetic silencing of paxillin blocked neuritogenesis, just like Nckβ knockdown. Reintroducing a nondegradable Nckβ into Nckβ short interfering RNA-expressing PC12 cells rescued paxillin from down-regulation and allowed the resumption of neuritogenesis. Forced expression of paxillin in Nckβ knockdown PC12 also rescued its capacity for neuritogenesis. Finally, Nckβ, but not Nckα, binds strongly to paxillin and treatment of the neurons with proteosome inhibitors prevented paxillin down-regulation in Nckβ knockdown neurons. Thus, Nckβ maintains paxillin stability during neuritogenesis.

scholarly journals The role of FLOWERING LOCUS C in vernalization of Brassica: the importance of vernalization research in the face of climate change

2018 ◽  
Vol 69 (1) ◽  
pp. 30 ◽  
Author(s):  
Daniel J. Shea ◽  
Etsuko Itabashi ◽  
Satoko Takada ◽  
Eigo Fukai ◽  
Tomohiro Kakizaki ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Model Organism ◽  
Climatic Changes ◽  
Environmental Cues ◽  
Plant Responses ◽  
Agricultural Crops ◽  
Regulatory Pathways ◽  
Evolutionarily Conserved ◽  
The Face

As climatic changes occur over the coming decades, our scientific understanding of plant responses to environmental cues will become an increasingly important consideration in the breeding of agricultural crops. This review provides a summary of the literature regarding vernalization research in Brassicaceae, covering both the historical origins of vernalization research and current understanding of the molecular mechanisms behind the regulatory pathways involved in vernalization and subsequent inflorescence. We discuss the evolutionarily conserved biology between the model organism Arabidopsis thaliana and the Brassica genus of crop cultivars and contrast the differences between the genera to illustrate the importance of Brassica-specific research into vernalization.

scholarly journals Autophagy in unicellular eukaryotes

2010 ◽  
Vol 365 (1541) ◽  
pp. 819-830 ◽  
Author(s):  
Jan A. K. W. Kiel
Keyword(s):  
Molecular Mechanisms ◽  
Yeast Species ◽  
Developmental Change ◽  
Building Blocks ◽  
Extracellular Medium ◽  
New Host ◽  
Growth And Survival ◽  
Atp Production ◽  
Unicellular Eukaryotes

Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.

scholarly journals Dietary Melatonin Supplementation Could Be a Promising Preventing/Therapeutic Approach for a Variety of Liver Diseases

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1135 ◽  
Author(s):  
Francesca Bonomini ◽  
Elisa Borsani ◽  
Gaia Favero ◽  
Luigi Rodella ◽  
Rita Rezzani
Keyword(s):  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Therapeutic Strategies ◽  
Beneficial Effects ◽  
Pathological Conditions ◽  
Positive Effect ◽  
And Oxidative Stress

In the therapeutic strategies, the role of diet is a well-established factor that can also have an important role in liver diseases. Melatonin, identified in animals, has many antioxidant properties and it was after discovered also in plants, named phytomelatonin. These substances have a positive effect during aging and in pathological conditions too. In particular, it is important to underline that the amount of melatonin produced by pineal gland in human decreases during lifetime and its reduction in blood could be related to pathological conditions in which mitochondria and oxidative stress play a pivotal role. Moreover, it has been indicated that melatonin/phytomelatonin containing foods may provide dietary melatonin, so their ingestion through balanced diets could be sufficient to confer health benefits. In this review, the classification of liver diseases and an overview of the most important aspects of melatonin/phytomelatonin, concerning the differences among their synthesis, their presence in foods and their role in health and diseases, are summarized. The findings suggest that melatonin/phytomelatonin supplementation with diet should be considered important in preventing different disease settings, in particular in liver. Currently, more studies are needed to strengthen the potential beneficial effects of melatonin/phytomelatonin in liver diseases and to better clarify the molecular mechanisms of action.

scholarly journals Tribbles in normal and malignant haematopoiesis

2015 ◽  
Vol 43 (5) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sarah J. Stein ◽  
Ethan A. Mack ◽  
Kelly S. Rome ◽  
Warren S. Pear
Keyword(s):  
E3 Ligase ◽  
Cell Types ◽  
Protein Family ◽  
Conserved Motifs ◽  
Tissue Specific ◽  
Cellular Events ◽  
Haematopoietic Cells ◽  
Evolutionarily Conserved ◽  
Multiple Cell

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types.

scholarly journals Regulation of TRH neurons and energy homeostasis-related signals under stress

2015 ◽  
Vol 224 (3) ◽  
pp. R139-R159 ◽  
Author(s):  
Patricia Joseph-Bravo ◽  
Lorraine Jaimes-Hoy ◽  
Jean-Louis Charli
Keyword(s):  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cellular Phenotype ◽  
Energy Demands ◽  
Rapid Responses ◽  
Hpt Axis

Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo–pituitary–thyroid (HPT) and hypothalamo–pituitary–adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription ofTrhin vivoandin vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

scholarly journals Recent progress in research on molecular mechanisms of autophagy in the heart

2015 ◽  
Vol 308 (4) ◽  
pp. H259-H268 ◽  
Author(s):  
Yasuhiro Maejima ◽  
Yun Chen ◽  
Mitsuaki Isobe ◽  
Åsa B. Gustafsson ◽  
Richard N. Kitsis ◽  
...  
Keyword(s):  
Heart Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Degradation Process ◽  
Structure And Function ◽  
Cellular Functions ◽  
Evolutionarily Conserved ◽  
And Function ◽  
Cellular Dysfunction

Dysregulation of autophagy, an evolutionarily conserved process for degradation of long-lived proteins and organelles, has been implicated in the pathogenesis of human disease. Recent research has uncovered pathways that control autophagy in the heart and molecular mechanisms by which alterations in this process affect cardiac structure and function. Although initially thought to be a nonselective degradation process, autophagy, as it has become increasingly clear, can exhibit specificity in the degradation of molecules and organelles, such as mitochondria. Furthermore, it has been shown that autophagy is involved in a wide variety of previously unrecognized cellular functions, such as cell death and metabolism. A growing body of evidence suggests that deviation from appropriate levels of autophagy causes cellular dysfunction and death, which in turn leads to heart disease. Here, we review recent advances in understanding the role of autophagy in heart disease, highlight unsolved issues, and discuss the therapeutic potential of modulating autophagy in heart disease.

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