scholarly journals Diverse Functions of Tim50, a Component of the Mitochondrial Inner Membrane Protein Translocase

2021 ◽  
Vol 22 (15) ◽  
pp. 7779
Author(s):  
Minu Chaudhuri ◽  
Anuj Tripathi ◽  
Fidel Soto Gonzalez
Keyword(s):  
Protein Complexes ◽  
Cellular Functions ◽  
Mitochondrial Structure ◽  
Structure And Dynamics ◽  
Unicellular Eukaryotes ◽  
Mitochondrial Inner Membrane ◽  
Receptor Component ◽  
Inner Membrane Protein ◽  
Multicellular Organisms

Mitochondria are essential in eukaryotes. Besides producing 80% of total cellular ATP, mitochondria are involved in various cellular functions such as apoptosis, inflammation, innate immunity, stress tolerance, and Ca2+ homeostasis. Mitochondria are also the site for many critical metabolic pathways and are integrated into the signaling network to maintain cellular homeostasis under stress. Mitochondria require hundreds of proteins to perform all these functions. Since the mitochondrial genome only encodes a handful of proteins, most mitochondrial proteins are imported from the cytosol via receptor/translocase complexes on the mitochondrial outer and inner membranes known as TOMs and TIMs. Many of the subunits of these protein complexes are essential for cell survival in model yeast and other unicellular eukaryotes. Defects in the mitochondrial import machineries are also associated with various metabolic, developmental, and neurodegenerative disorders in multicellular organisms. In addition to their canonical functions, these protein translocases also help maintain mitochondrial structure and dynamics, lipid metabolism, and stress response. This review focuses on the role of Tim50, the receptor component of one of the TIM complexes, in different cellular functions, with an emphasis on the Tim50 homologue in parasitic protozoan Trypanosoma brucei.

scholarly journals Two Intermembrane Space Tim Complexes Interact with Different Domains of Tim23p during Its Import into Mitochondria

2000 ◽  
Vol 150 (6) ◽  
pp. 1271-1282 ◽  
Author(s):  
Alison J. Davis ◽  
Naresh B. Sepuri ◽  
Jason Holder ◽  
Arthur E. Johnson ◽  
Robert E. Jensen
Keyword(s):  
Protein Complexes ◽  
Intermediate Stage ◽  
Terminal Segment ◽  
Mitochondrial Outer Membrane ◽  
Cross Linking ◽  
Intermembrane Space ◽  
Cross Link ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

Tim23p (translocase of the inner membrane) is an essential import component located in the mitochondrial inner membrane. To determine how the Tim23 protein itself is transported into mitochondria, we used chemical cross-linking to identify proteins adjacent to Tim23p during its biogenesis. In the absence of an inner membrane potential, Tim23p is translocated across the mitochondrial outer membrane, but not inserted into the inner membrane. At this intermediate stage, we find that Tim23p forms cross-linked products with two distinct protein complexes of the intermembrane space, Tim8p–Tim13p and Tim9p–Tim10p. Tim9p and Tim10p cross-link to the COOH-terminal domain of the Tim23 protein, which carries all of the targeting signals for Tim23p. Therefore, our results suggest that the Tim9p–Tim10p complex plays a key role in Tim23p import. In contrast, Tim8p and Tim13p cross-link to the hydrophilic NH2-terminal segment of Tim23p, which does not carry essential import information and, thus, the role of Tim8p–Tim13p is unclear. Tim23p contains two matrix-facing, positively charged loops that are essential for its insertion into the inner membrane. The positive charges are not required for interaction with the Tim9p–Tim10p complex, but are essential for cross-linking of Tim23p to components of the inner membrane insertion machinery, including Tim54p, Tim22p, and Tim12p.

scholarly journals Super-resolution microscopy reveals arrangement of inner membrane protein complexes in mammalian mitochondria

2021 ◽  
Author(s):  
Catherine S. Palmer ◽  
Jieqiong Lou ◽  
Betty Kouskousis ◽  
Elvis Pandzic ◽  
Alexander J. Anderson ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Protein Complexes ◽  
Super Resolution ◽  
Bimodal Distribution ◽  
Complex Iv ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Cellular Context ◽  
Inner Membrane Protein ◽  
Super Resolution Microscopy

The mitochondrial inner membrane is a protein rich environment containing large multimeric complexes including complexes of the mitochondrial electron transport chain, mitochondrial translocases and quality control machineries. Although the inner membrane is highly proteinaceous, with 40–60% of all mitochondrial proteins localised to this compartment, little is known about the spatial distribution and organisation of complexes in this environment. We set out to survey the arrangement of inner membrane complexes using stochastic optical reconstruction microscopy (STORM). We show subunits of the TIM23 Complex, Tim23 and Tim44, and the Complex IV subunit COXIV form organised clusters and show distinct properties to the outer membrane protein Tom20. Density based cluster analysis indicated a bimodal distribution of Tim44 that is distinct from Tim23, suggesting distinct TIM23 subcomplexes. COXIV is arranged in larger clusters, that are disrupted upon disruption of Complex IV assembly. Thus, STORM super-resolution microscopy is a powerful approach to examine the nanoscale distribution of mitochondrial inner membrane complexes, providing a “visual” approach to obtaining pivotal information on how mitochondrial complexes exist in a cellular context.

scholarly journals Lipid Microdomains in Cell Nucleus

2008 ◽  
Vol 19 (12) ◽  
pp. 5289-5295 ◽  
Author(s):  
Giacomo Cascianelli ◽  
Maristella Villani ◽  
Marcello Tosti ◽  
Francesca Marini ◽  
Elisa Bartoccini ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Lipid Composition ◽  
Protein Complexes ◽  
Membrane Microdomains ◽  
Cellular Functions ◽  
Transcription Process ◽  
Lipid Protein Interactions ◽  
First Time ◽  
Specific Lipid

It is known that nuclear lipids play a role in proliferation, differentiation, and apoptotic process. Cellular nuclei contain high levels of phosphatidylcholine and sphingomyelin, which are partially linked with cholesterol and proteins to form lipid–protein complexes. These lipids are also associated with transcription factors and newly synthesized RNA but, up to date, their organization is still unknown. The aim of the present work was to study if these specific lipid–protein interactions could be nuclear membrane microdomains and to evaluate their possible role. The results obtained demonstrate for the first time the existence of nuclear microdomains characterized by a specific lipid composition similar to that of intranuclear lipid–protein complexes previously described. Nuclear microdomain lipid composition changes during cell proliferation when the content of newly synthesized RNA increases. Because previous data show a correlation between nuclear lipids and transcription process, the role of nuclear microdomains in cellular functions is discussed.

scholarly journals Isoform-Specific Localization of A-RAF in Mitochondria

2000 ◽  
Vol 20 (13) ◽  
pp. 4870-4878 ◽  
Author(s):  
Anton Yuryev ◽  
Makoto Ono ◽  
Stephen A. Goff ◽  
Frank Macaluso ◽  
Lawrence P. Wennogle
Keyword(s):  
Protein Interactions ◽  
Protein Import ◽  
Liver Mitochondria ◽  
Transport Systems ◽  
Rat Liver Mitochondria ◽  
Cellular Transport ◽  
Cellular Functions ◽  
Specific Localization ◽  
Inner Membrane Protein

ABSTRACT RAF kinase is a family of isoforms including A-RAF, B-RAF, and C-RAF. Despite the important role of RAF in cell growth and proliferation, little evidence exists for isoform-specific function of RAF family members. Using Western analysis and immunogold labeling, A-RAF was selectively localized in highly purified rat liver mitochondria. Two novel human proteins, which interact specifically with A-RAF, were identified, and the full-length sequences are reported. These proteins, referred to as hTOM and hTIM, are similar to components of mitochondrial outer and inner membrane protein-import receptors from lower organisms, implicating their involvement in the mitochondrial transport of A-RAF. hTOM contains multiple tetratricopeptide repeat (TPR) domains, which function in protein-protein interactions. TPR domains are frequently present in proteins involved in cellular transport systems. In contrast, protein 14-3-3, an abundant cytosolic protein that participates in many facets of signal transduction, was found to interact with C-RAF but not with A-RAF N-terminal domain. This information is discussed in view of the important role of mitochondria in cellular functions involving energy balance, proliferation, and apoptosis and the potential role of A-RAF in regulating these systems.

scholarly journals Functional roles of Mg2+ binding sites in ion-dependent gating of a Mg2+ channel, MgtE, revealed by solution NMR

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Tatsuro Maruyama ◽  
Shunsuke Imai ◽  
Tsukasa Kusakizako ◽  
Motoyuki Hattori ◽  
Ryuichiro Ishitani ◽  
...  
Keyword(s):  
Binding Sites ◽  
Divalent Cations ◽  
Solution Nmr ◽  
Resonance Spectroscopy ◽  
Wild Type ◽  
Cellular Functions ◽  
Functional Roles ◽  
Structure And Dynamics ◽  
Mutant Forms

Magnesium ions (Mg2+) are divalent cations essential for various cellular functions. Mg2+ homeostasis is maintained through Mg2+ channels such as MgtE, a prokaryotic Mg2+ channel whose gating is regulated by intracellular Mg2+ levels. Our previous crystal structure of MgtE in the Mg2+-bound, closed state revealed the existence of seven crystallographically-independent Mg2+-binding sites, Mg1–Mg7. The role of Mg2+-binding to each site in channel closure remains unknown. Here, we investigated Mg2+-dependent changes in the structure and dynamics of MgtE using nuclear magnetic resonance spectroscopy. Mg2+-titration experiments, using wild-type and mutant forms of MgtE, revealed that the Mg2+ binding sites Mg1, Mg2, Mg3, and Mg6, exhibited cooperativity and a higher affinity for Mg2+, enabling the remaining Mg2+ binding sites, Mg4, Mg5, and Mg7, to play important roles in channel closure. This study revealed the role of each Mg2+-binding site in MgtE gating, underlying the mechanism of cellular Mg2+ homeostasis.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

ІНТЕРПРЕТАЦІЯ КАТЕГОРІЇ РОЗВИТКУ В СУЧАСНІЙ ПСИХОЛОГІЇ

1970 ◽  
Vol 8 (1) ◽  
pp. 22-30
Author(s):  
Анжеліка Шамне
Keyword(s):  
Cultural Context ◽  
Developmental Psychology ◽  
Structure And Dynamics ◽  
Modern Psychology ◽  
Development Site ◽  
Approaches To Study ◽  
Methodological Approaches ◽  
Self Motion

У статті розглянуто сучасні підходи до інтерпретації категорії розвитку, розкрито теоретичні  та методологічні підходи до вивчення категорії розвитку у сучасній психології, визначено її психологічний  зміст,   моделі,   структуру   та   динаміку.   Категорія   розвитку   розглядається   як   епіцентр   наукової  проблематики у психології та як поняття інтегративного типу. Розвиток проаналізовано як категорію,  явище і проблему психології розвитку в різних аспектах аналізу. Розглянуто місце розвитку в системі  споріднених психологічних понять. У статті також аналізуються психологічні аспекти теоретичних та  методологічних  постнекласичних  тенденцій  вивчення  природи,  характеру  та  визначення  психічного  розвитку. Постнекласична парадигма та плюралістична методологія пізнання визначають розмитість  дисциплінарної мови  та  врахування  ролі  соціокультурного  контексту  при  вивченні  психологічних явищ.  Важливими тенденціями сучасного теоретико-методологічного стану психологічних досліджень розвитку  також є визнання неефективності моністичного підходу до його вивчення, взаємозв'язок теоретичних ідей  та   спроби   створення   метатеоретичних   схем,   постнекласичне   розуміння   розвитку   як   принципово  незавершеного   процесу   саморуху,   актуалізація   антропологічного   діапазону   проблем   та   посилення  спрямованості на роль культурного контексту в дослідженні розвитку людини.  The article deals with the modern approaches to the interpretation of the category of development, reveals  the theoretical and methodological approaches to study of development in modern psychology, its psychological  content, patterns, structure and dynamics. Category of development is viewed as an epicenter of scientific issues in  modern  psychology  and  the  concept  of  the  integrative  type.  Category  of  development  is  considered  as  the  phenomenon  and  the  problem  of  developmental  psychology  in  various  aspects  of  the  analysis.  Analyzed  the  development site in the related psychological concepts. The article analyzes the psychological aspects of theoretical  and methodological postnonclassical contemporary trends in the study of nature, character, and determination of  mental  development.  Postnonclassical  paradigm  and  pluralistic  methodology  of  knowledge  determine  the  disciplinary blurring and increase of the role of the analysis of socio-cultural context in the study of psychological  phenomenon. The important tendencies of modern theoretical and methodological state of psychological researches  of development are facts of inefficiency of the monistic approach to its study, interconnection of theoretical ideas  and   attempts   of  creating   metatheoretical   schemes,   postnonclassical   understanding   of   development   as   a  fundamentally  uncompleted  process  of  self-motion,  actualization  of  anthropological  range  of  problems  and  strengthening of focus on the role of cultural context in research of human development.   

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

scholarly journals Carcinoma-associated fibroblasts derived exosomes modulate breast cancer cell stemness through exonic circHIF1A by miR-580-5p in hypoxic stress

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yanxia Zhan ◽  
Junxian Du ◽  
Zhihui Min ◽  
Li Ma ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Breast Cancer Cells ◽  
Hypoxic Stress ◽  
Cellular Functions ◽  
Breast Cancer Therapy ◽  
Array Analysis ◽  
Cancer Stroma ◽  
Carcinoma Associated Fibroblasts

AbstractHypoxia is a common phenomenon in solid tumors. The roles of exosomes from hypoxic breast cancer stroma are less studied. So, the study was aimed to investigate the role of exosomes from hypoxic cancer-associated fibroblasts (CAFs) cells in breast cancer. The circRNA array analysis was performed to screen differential expressed circRNAs between hypoxic and normoxic CAFs exosomes. Candidate circHIF1A (circ_0032138) was screened out and it was confirmed that circHIF1A was up-regulated in the exosomes from hypoxic CAFs and their exosomes. Through investigating cellular functions including cell proliferation and stem cell features, it was demonstrated that hypoxic CAFs exosomes transferred circHIF1A into breast cancer cells, which played an important role in cancer stem cell properties sponging miR-580-5p by regulating CD44 expression. In a summary, circHIF1A from hypoxic CAFs exosomes played an important role in stem cell properties of breast cancer. CircHIF1A may act as a target molecule of breast cancer therapy.

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.

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