scholarly journals Disentangling the biological information encoded in disordered mitochondrial morphology through its rapid elicitation by iCMM

2020 ◽  
Author(s):  
Takafumi Miyamoto ◽  
Hideki Uosaki ◽  
Yuhei Mizunoe ◽  
Satoi Goto ◽  
Daisuke Yamanaka ◽  
...  
Keyword(s):  
Genetic Engineering ◽  
Morphological Changes ◽  
Biological Significance ◽  
Biological Information ◽  
Mitochondrial Morphology ◽  
Cellular Functions ◽  
Health And Disease ◽  
Novel Method ◽  
Morphological Patterns

AbstractMitochondrial morphology is dynamically changed in conjunction with spatiotemporal functionality. Although considerable efforts have been made to understand why abnormal mitochondrial morphology occurs in various diseases, the biological significance of mitochondrial morphology in states of health and disease remains to be elucidated owing to technical limitations. In the present study, we developed a novel method, termed inducible Counter Mitochondrial Morphology (iCMM), to purposely manipulate mitochondrial morphological patterns on a minutes timescale, using a chemically inducible dimerization system. Using iCMM, we showed that mitochondrial morphological changes rapidly lead to the characteristic reconstitution of various biological information, which is difficult to investigate by conventional genetic engineering. The manipulation of mitochondrial morphology using iCMM can improve our understanding of the interplay between mitochondrial morphology and cellular functions.

scholarly journals Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers

2020 ◽  
Vol 21 (7) ◽  
pp. 2514 ◽  
Author(s):  
Pasquale Simeone ◽  
Giuseppina Bologna ◽  
Paola Lanuti ◽  
Laura Pierdomenico ◽  
Maria Teresa Guagnano ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biological Significance ◽  
Biological Information ◽  
Intercellular Signaling ◽  
Signal Transducers ◽  
Shuttle Vectors ◽  
Disease Biomarkers ◽  
Neural Communication ◽  
Health And Disease ◽  
Multicellular Organisms

Extracellular vesicles act as shuttle vectors or signal transducers that can deliver specific biological information and have progressively emerged as key regulators of organized communities of cells within multicellular organisms in health and disease. Here, we survey the evolutionary origin, general characteristics, and biological significance of extracellular vesicles as mediators of intercellular signaling, discuss the various subtypes of extracellular vesicles thus far described and the principal methodological approaches to their study, and review the role of extracellular vesicles in tumorigenesis, immunity, non-synaptic neural communication, vascular-neural communication through the blood-brain barrier, renal pathophysiology, and embryo-fetal/maternal communication through the placenta.

Correlation Between Cellular Functions and Morphological Changes of Human Trophoblast in Vitro

1975 ◽  
Vol 33 ◽  
pp. 600-601
Author(s):  
John C. Garancis ◽  
Robert O. Hussa ◽  
Michael T. Story ◽  
Donald Yorde ◽  
Roland A. Pattillo
Keyword(s):  
Electron Microscopy ◽  
Cellular Proliferation ◽  
Morphological Changes ◽  
Culture Fluid ◽  
Cellular Functions ◽  
Human Trophoblast ◽  
Transmission Electron ◽  
Marked Activity ◽  
Malignant Trophoblast

Human malignant trophoblast cells in continuous culture were incubated for 3 days in medium containing 1 mM N6-O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (dibutyryl cyclic AMP) and 1 mM theophylline. The culture fluid was replenished daily. Stimulated cultures secreted many times more chorionic gonadotropin and estrogens than did control cultures in the absence of increased cellular proliferation. Scanning electron microscopy revealed remarkable surface changes of stimulated cells. Control cells (not stimulated) were smooth or provided with varying numbers of microvilli (Fig. 1). The latter, usually, were short and thin. The surface features of stimulated cells were considerably different. There was marked increase of microvilli which appeared elongated and thick. Many cells were covered with confluent polypoid projections (Fig. 2). Transmission electron microscopy demonstrated marked activity of cytoplasmic organelles. Mitochondria were increased in number and size; some giant forms with numerous cristae were observed.

Neuroligin-2 as a central organizer of inhibitory synapses in health and disease

2020 ◽  
Vol 13 (663) ◽  
pp. eabd8379
Author(s):  
Heba Ali ◽  
Lena Marth ◽  
Dilja Krueger-Burg
Keyword(s):  
Synaptic Transmission ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Inhibitory Synapses ◽  
Molecular Architecture ◽  
Cellular Functions ◽  
Altered Expression ◽  
Health And Disease ◽  
Flow Of Information

Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

scholarly journals MITOCHONDRIAL BIOGENESIS DURING DIFFERENTIATION OF ARTEMIA SALINA CYSTS

1973 ◽  
Vol 58 (3) ◽  
pp. 643-649 ◽  
Author(s):  
H. Schmitt ◽  
H. Grossfeld ◽  
U. Z. Littauer
Keyword(s):  
Cytochrome C ◽  
Cytochrome Oxidase ◽  
Cytochrome B ◽  
Mitochondrial Biogenesis ◽  
Brine Shrimp ◽  
Morphological Changes ◽  
Artemia Salina ◽  
Mitochondrial Morphology ◽  
Second Stage ◽  
Two Stages

Mitochondria isolated from cysts of Artemia salina (brine shrimp) were found to be devoid of cristae and to possess a low respiratory capability. Hydration of the cysts induces marked biochemical and morphological changes in the mitochondria. Their biogenesis proceeds in two stages. The first stage is completed within 1 h and is characterized by a rapid increase in the respiratory capability of the mitochondria, their cytochrome oxidase, cytochrome b, cytochrome c and perhaps some morphological changes. In the second stage there is an increase in the protein-synthesizing capacity of the mitochondria as well as striking changes in mitochondrial morphology leading to the formation of cristae.

scholarly journals Mito Hacker: a set of tools to enable high-throughput analysis of mitochondrial network morphology

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ali Rohani ◽  
Jennifer A. Kashatus ◽  
Dane T. Sessions ◽  
Salma Sharmin ◽  
David F. Kashatus
Keyword(s):  
Single Cell ◽  
High Throughput ◽  
Data Science ◽  
Structural Information ◽  
Morphological Changes ◽  
Mitochondrial Morphology ◽  
Single Cell Level ◽  
Mitochondrial Network ◽  
Cell Level ◽  
Wide Range

Abstract Mitochondria are highly dynamic organelles that can exhibit a wide range of morphologies. Mitochondrial morphology can differ significantly across cell types, reflecting different physiological needs, but can also change rapidly in response to stress or the activation of signaling pathways. Understanding both the cause and consequences of these morphological changes is critical to fully understanding how mitochondrial function contributes to both normal and pathological physiology. However, while robust and quantitative analysis of mitochondrial morphology has become increasingly accessible, there is a need for new tools to generate and analyze large data sets of mitochondrial images in high throughput. The generation of such datasets is critical to fully benefit from rapidly evolving methods in data science, such as neural networks, that have shown tremendous value in extracting novel biological insights and generating new hypotheses. Here we describe a set of three computational tools, Cell Catcher, Mito Catcher and MiA, that we have developed to extract extensive mitochondrial network data on a single-cell level from multi-cell fluorescence images. Cell Catcher automatically separates and isolates individual cells from multi-cell images; Mito Catcher uses the statistical distribution of pixel intensities across the mitochondrial network to detect and remove background noise from the cell and segment the mitochondrial network; MiA uses the binarized mitochondrial network to perform more than 100 mitochondria-level and cell-level morphometric measurements. To validate the utility of this set of tools, we generated a database of morphological features for 630 individual cells that encode 0, 1 or 2 alleles of the mitochondrial fission GTPase Drp1 and demonstrate that these mitochondrial data could be used to predict Drp1 genotype with 87% accuracy. Together, this suite of tools enables the high-throughput and automated collection of detailed and quantitative mitochondrial structural information at a single-cell level. Furthermore, the data generated with these tools, when combined with advanced data science approaches, can be used to generate novel biological insights.

scholarly journals Toward a better understanding of folate metabolism in health and disease

2018 ◽  
Vol 216 (2) ◽  
pp. 253-266 ◽  
Author(s):  
Yuxiang Zheng ◽  
Lewis C. Cantley
Keyword(s):  
Cell Proliferation ◽  
Epigenetic Regulation ◽  
Historical Perspective ◽  
Mitochondrial Protein ◽  
Protein Translation ◽  
Folate Metabolism ◽  
Cellular Functions ◽  
Biochemical Processes ◽  
Health And Disease ◽  
Thymidine Monophosphate

Folate metabolism is crucial for many biochemical processes, including purine and thymidine monophosphate (dTMP) biosynthesis, mitochondrial protein translation, and methionine regeneration. These biochemical processes in turn support critical cellular functions such as cell proliferation, mitochondrial respiration, and epigenetic regulation. Not surprisingly, abnormal folate metabolism has been causally linked with a myriad of diseases. In this review, we provide a historical perspective, delve into folate chemistry that is often overlooked, and point out various missing links and underdeveloped areas in folate metabolism for future exploration.

scholarly journals Identification of Interorganellar Crosstalk Effect on Various Diseases, Including Kidney Disease: A Systematic Review and Meta-analysis

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Fateme Shamekhi Amiri
Keyword(s):  
Relative Risk ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Data Sources ◽  
Cellular Functions ◽  
Pubmed Central ◽  
Subcellular Organelles ◽  
Age Related ◽  
Health And Disease

Context: Subcellular organelles communicate with each other via their metabolites and maintain different cellular functions. They contain nucleus, mitochondria, endoplasmic reticulum, peroxisomes, and lysosomes. Objectives: This study aimed to identify interorganellar communication (crosstalk) in physiopathological states of cells in health and disease. Data Sources: The databases including PubMed Central, Embase, Scopus, and Google Scholar were searched to extract data. For statistical analyses, percentage, relative risk, and odds ratio were used. Moreover, the risk of bias was assessed by Cochrane collaboration’s tool. Results: Out of 20 studies included in this research, 12 (60%) studies included mitochondria-ER communication, 4 (20%) studies mitochondria-lysosome communication, 2 (10%) studies mitochondria-peroxisome, and 2 (10%) studies mitochondria-nucleus. Interorganellar crosstalk between mitochondria and peroxisome or lysosome had risk and odds of 1.5 (effect) on aging and age-related disorders. There were no effects of mitochondrial communication with other organelles on certain pathologies. The relative risk of mitochondria to nucleus crosstalk on apoptosis was assessed 1.13, and relative risk of mitochondria to lysosome crosstalk was assessed 2. In addition, the odds ratio of mitochondria to lysosome crosstalk on apoptosis was assessed 5, indicating a large effect on this crosstalk. Conclusions: Recent expansion of pharmacological, molecular, and genetic tools indicated these organelles have active intracellular and extracellular communications, which is important for cells and organ homeostasis. Disruption of such communication has been associated with aging and age-related disorders in this research.

scholarly journals The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex

2021 ◽  
Author(s):  
Subramaniyam Ravichandran ◽  
Maria Razzaq ◽  
Nazia Parveen ◽  
Ambarnil Ghosh ◽  
Kyeong Kyu Kim
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Biological Significance ◽  
Cellular Functions ◽  
Hairpin Loops ◽  
G Quadruplex ◽  
Reporter Assays ◽  
Expression Activity ◽  
The Stability ◽  
And Function

Abstract G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

scholarly journals Identification of Fis1 Interactors in Toxoplasma gondii Reveals a Novel Protein Required for Peripheral Distribution of the Mitochondrion

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kylie Jacobs ◽  
Robert Charvat ◽  
Gustavo Arrizabalaga
Keyword(s):  
Life Cycle ◽  
Toxoplasma Gondii ◽  
Morphological Changes ◽  
Dominant Negative Effect ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Content Type ◽  
Membrane Contact Sites ◽  
Intracellular Parasites ◽  
Single Mitochondrion

ABSTRACT Toxoplasma gondii’s single mitochondrion is very dynamic and undergoes morphological changes throughout the parasite’s life cycle. During parasite division, the mitochondrion elongates, enters the daughter cells just prior to cytokinesis, and undergoes fission. Extensive morphological changes also occur as the parasite transitions from the intracellular environment to the extracellular environment. We show that treatment with the ionophore monensin causes reversible constriction of the mitochondrial outer membrane and that this effect depends on the function of the fission-related protein Fis1. We also observed that mislocalization of the endogenous Fis1 causes a dominant-negative effect that affects the morphology of the mitochondrion. As this suggests that Fis1 interacts with proteins critical for maintenance of mitochondrial structure, we performed various protein interaction trap screens. In this manner, we identified a novel outer mitochondrial membrane protein, LMF1, which is essential for positioning of the mitochondrion in intracellular parasites. Normally, while inside a host cell, the parasite mitochondrion is maintained in a lasso shape that stretches around the parasite periphery where it has regions of coupling with the parasite pellicle, suggesting the presence of membrane contact sites. In intracellular parasites lacking LMF1, the mitochondrion is retracted away from the pellicle and instead is collapsed, as normally seen only in extracellular parasites. We show that this phenotype is associated with defects in parasite fitness and mitochondrial segregation. Thus, LMF1 is necessary for mitochondrial association with the parasite pellicle during intracellular growth, and proper mitochondrial morphology is a prerequisite for mitochondrial division. IMPORTANCE Toxoplasma gondii is an opportunistic pathogen that can cause devastating tissue damage in the immunocompromised and congenitally infected. Current therapies are not effective against all life stages of the parasite, and many cause toxic effects. The single mitochondrion of this parasite is a validated drug target, and it changes its shape throughout its life cycle. When the parasite is inside a cell, the mitochondrion adopts a lasso shape that lies in close proximity to the pellicle. The functional significance of this morphology is not understood and the proteins involved are currently not known. We have identified a protein that is required for proper mitochondrial positioning at the periphery and that likely plays a role in tethering this organelle. Loss of this protein results in dramatic changes to the mitochondrial morphology and significant parasite division and propagation defects. Our results give important insight into the molecular mechanisms regulating mitochondrial morphology.

scholarly journals Dietary microRNA—A Novel Functional Component of Food

2019 ◽  
Vol 10 (4) ◽  
pp. 711-721 ◽  
Author(s):  
Lin Zhang ◽  
Ting Chen ◽  
Yulong Yin ◽  
Chen-Yu Zhang ◽  
Yong-Liang Zhang
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Biological Significance ◽  
Circulatory System ◽  
Physiological Effects ◽  
Biological Processes ◽  
Regulate Gene Expression ◽  
Functional Component ◽  
Health And Disease ◽  
Regulate Gene

ABSTRACT MicroRNAs are a class of small RNAs that play essential roles in various biological processes by silencing genes. Evidence emerging in recent years suggests that microRNAs in food can be absorbed into the circulatory system and organs of humans and other animals, where they regulate gene expression and biological processes. These food-derived dietary microRNAs may serve as a novel functional component of food, a role that has been neglected to date. However, a significant amount of evidence challenges this new concept. The absorption, stability, and physiological effects of dietary microRNA in recipients, especially in mammals, are currently under heavy debate. In this review, we summarize our current understanding of the unique characteristics of dietary microRNAs and concerns about both the mechanistic and methodological basis for studying the biological significance of dietary microRNAs. Such efforts will benefit continuing investigations and offer new perspectives for the interpretation of the roles of dietary microRNA with respect to the health and disease of humans and animals.

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