scholarly journals Mitochondrial DNA: an advance in eukaryotic cell biology in the 1960s

2005 ◽  
Vol 97 (9) ◽  
pp. 743-748 ◽  
Author(s):  
Jean-Claude Mounolou ◽  
François Lacroute
Keyword(s):  
Mitochondrial Dna ◽  
Cell Biology ◽  
Eukaryotic Cell ◽  
The 1960S

scholarly journals PAK and other Rho-associated kinases – effectors with surprisingly diverse mechanisms of regulation

2005 ◽  
Vol 386 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Zhou-shen ZHAO ◽  
Ed MANSER
Keyword(s):  
Rho Gtpases ◽  
Cell Biology ◽  
Rho Gtpase ◽  
Rho Kinase ◽  
Molecular Switches ◽  
Eukaryotic Cell ◽  
Effector Proteins ◽  
Downstream Effector ◽  
P21 Activated Kinase ◽  
Do So

The Rho GTPases are a family of molecular switches that are critical regulators of signal transduction pathways in eukaryotic cells. They are known principally for their role in regulating the cytoskeleton, and do so by recruiting a variety of downstream effector proteins. Kinases form an important class of Rho effector, and part of the biological complexity brought about by switching on a single GTPase results from downstream phosphorylation cascades. Here we focus on our current understanding of the way in which different Rho-associated serine/threonine kinases, denoted PAK (p21-activated kinase), MLK (mixed-lineage kinase), ROK (Rho-kinase), MRCK (myotonin-related Cdc42-binding kinase), CRIK (citron kinase) and PKN (protein kinase novel), interact with and are regulated by their partner GTPases. All of these kinases have in common an ability to dimerize, and in most cases interact with a variety of other proteins that are important for their function. A diversity of known structures underpin the Rho GTPase–kinase interaction, but only in the case of PAK do we have a good molecular understanding of kinase regulation. The ability of Rho GTPases to co-ordinate spatial and temporal phosphorylation events explains in part their prominent role in eukaryotic cell biology.

Cytosolic and mitochondrial Hsp90 in cytokinesis, mitochondrial DNA replication, and drug action in Trypanosoma brucei

2021 ◽  
Author(s):  
Kirsten J. Meyer ◽  
Theresa A. Shapiro
Keyword(s):  
Mitochondrial Dna ◽  
Trypanosoma Brucei ◽  
Cell Biology ◽  
Drug Targets ◽  
Heat Shock Protein 90 ◽  
Cell Cycle Regulators ◽  
Hsp90 Inhibitors ◽  
African Trypanosomes ◽  
Hsp90 Activity

Trypanosoma brucei subspecies cause African sleeping sickness in humans, an infection that is commonly fatal if not treated, and available therapies are limited. Previous studies have shown that heat shock protein 90 (Hsp90) inhibitors have potent and vivid activity against bloodstream form trypanosomes. Hsp90s are phylogenetically conserved and essential catalysts that function at the crux of cell biology, where they ensure the proper folding of proteins and their assembly into multicomponent complexes. To assess the specificity of Hsp90 inhibitors and further define the role of Hsp90s in African trypanosomes, we used RNAi to knockdown cytosolic and mitochondrial Hsp90s (HSP83 and HSP84, respectively). Loss of either protein led to cell death but the phenotypes were distinctly different. Depletion of cytosolic HSP83 closely mimicked the consequences of chemically depleting Hsp90 activity with inhibitor 17-AAG. In these cells cytokinesis was severely disrupted and segregation of the kinetoplast (the massive mitochondrial DNA structure unique to this family of eukaryotic pathogens) was impaired, leading to cells with abnormal kDNA structures. Quite differently, knockdown of mitochondrial HSP84 did not impair cytokinesis but halted the initiation of new kDNA synthesis, generating cells without kDNA. These findings highlight the central role for Hsp90s in chaperoning cell cycle regulators in trypanosomes, reveal their unique function in kinetoplast replication, and reinforce their specificity and value as drug targets.

scholarly journals The road to rack and ruin: selecting deleterious mitochondrial DNA variants

2014 ◽  
Vol 369 (1646) ◽  
pp. 20130451 ◽  
Author(s):  
Ian J. Holt ◽  
Dave Speijer ◽  
Thomas B. L. Kirkwood
Keyword(s):  
Mitochondrial Dna ◽  
Energy Production ◽  
Rapid Change ◽  
Eukaryotic Cell ◽  
The Road ◽  
Cell Tissue ◽  
Dna Variants ◽  
A Cell ◽  
The Subject ◽  
Mitochondrial Dna Variants

Mitochondria constitute the major energy-producing compartment of the eukaryotic cell. These organelles contain many molecules of DNA that contribute only a handful of proteins required for energy production. Mutations in the DNA of mitochondria were identified as a cause of human disease a quarter of a century ago, and they have subsequently been implicated in ageing. The process whereby deleterious variants come to dominate a cell, tissue or human is the subject of debate. It is likely to involve multiple, often competing, factors, as selection pressures on mitochondrial DNA can be both indirect and intermittent, and are subjected to rapid change. Here, we assess the different models and the prospects for preventing the accumulation of deleterious mitochondrial DNA variants with time.

scholarly journals Biological switches and clocks

2008 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
John J Tyson ◽  
Reka Albert ◽  
Albert Goldbeter ◽  
Peter Ruoff ◽  
Jill Sible
Keyword(s):  
Cell Biology ◽  
Gene Networks ◽  
Cell Cycle Progression ◽  
Protein Interaction Networks ◽  
Special Issue ◽  
Synthetic Gene Networks ◽  
Cycle Progression ◽  
Molecular Cell Biology ◽  
1960S And 1970S ◽  
The 1960S

To introduce this special issue on biological switches and clocks, we review the historical development of mathematical models of bistability and oscillations in chemical reaction networks. In the 1960s and 1970s, these models were limited to well-studied biochemical examples, such as glycolytic oscillations and cyclic AMP signalling. After the molecular genetics revolution of the 1980s, the field of molecular cell biology was thrown wide open to mathematical modellers. We review recent advances in modelling the gene–protein interaction networks that control circadian rhythms, cell cycle progression, signal processing and the design of synthetic gene networks.

scholarly journals The autoregulation of a eukaryotic DNA transposon

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Corentin Claeys Bouuaert ◽  
Karen Lipkow ◽  
Steven S Andrews ◽  
Danxu Liu ◽  
Ronald Chalmers
Keyword(s):  
Binding Sites ◽  
Cell Biology ◽  
Eukaryotic Cell ◽  
Emergent Property ◽  
In Vivo Experiments ◽  
Constant Rate ◽  
Eukaryotic Dna ◽  
Transposase Expression

How do DNA transposons live in harmony with their hosts? Bacteria provide the only documented mechanisms for autoregulation, but these are incompatible with eukaryotic cell biology. Here we show that autoregulation of Hsmar1 operates during assembly of the transpososome and arises from the multimeric state of the transposase, mediated by a competition for binding sites. We explore the dynamics of a genomic invasion using a computer model, supported by in vitro and in vivo experiments, and show that amplification accelerates at first but then achieves a constant rate. The rate is proportional to the genome size and inversely proportional to transposase expression and its affinity for the transposon ends. Mariner transposons may therefore resist post-transcriptional silencing. Because regulation is an emergent property of the reaction it is resistant to selfish exploitation. The behavior of distantly related eukaryotic transposons is consistent with the same mechanism, which may therefore be widely applicable.

scholarly journals Probing connectivity between transcriptional and post-transcriptional gene networks

2011 ◽  
Vol 32 (4) ◽  
pp. 166
Author(s):  
Sarah E Boyd ◽  
Johnathon M Keith ◽  
Ana Traven ◽  
Traude Beilharz
Keyword(s):  
Complete Genome ◽  
Cell Biology ◽  
Gene Networks ◽  
Eukaryotic Cell ◽  
Current Understanding ◽  
Multidimensional Datasets ◽  
Growth Requirements ◽  
Genome Wide ◽  
Simple Growth

The foundation for much of our current understanding of eukaryotic cell biology stems from studies exploiting the combined power of this yeast?s genetic tractability and its simple growth requirements. Furthermore, access to an early complete genome in 1996 allowed yeast researchers to spearhead the move toward genome-wide studies that underpin our thinking about systems-level biology today. Indeed, the last decade has been so rich in these studies that it has become close to impossible for most biologists to interrogate the data in an unbiased fashion. The challenge for the next decade is to generate the informational tools to sort the multidimensional datasets for underlying networks.

scholarly journals Eukaryotic cell biology is temporally coordinated to support the energetic demands of protein homeostasis

2020 ◽  
Author(s):  
John S. O’Neill ◽  
Nathaniel P. Hoyle ◽  
J. Brian Robertson ◽  
Rachel S. Edgar ◽  
Andrew D. Beale ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Cell Biology ◽  
Protein Quality ◽  
Eukaryotic Cell ◽  
Protein Homeostasis ◽  
Cytosolic Ph ◽  
Dynamic Regulation ◽  
Temporal Regulation ◽  
Intrinsic Factors ◽  
Eukaryotic Proteomes

AbstractEvery aspect of yeast physiology is subject to robust temporal regulation, this becomes apparent under nutrient-limiting conditions 1-6 and results in biological oscillations whose function and mechanism is poorly resolved7. These yeast metabolic oscillations share features with circadian rhythms and typically interact with, but are independent of, the cell division cycle. Here we show that these cellular rhythms act to minimise energy expenditure by temporally restricting protein synthesis until sufficient cellular resources are present, whilst maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells initially ‘sequester and store’ metabolic resources such as carbohydrates, amino acids, K+ and other osmolytes; which accumulate via increased synthesis, transport, autophagy and biomolecular condensation that is stimulated by low glucose and cytosolic acidification. Replete stores trigger increased H+ export to elevate cytosolic pH, thereby stimulating TORC1 and liberating proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates a burst of increased protein synthesis, the liquidation of storage carbohydrates to sustain higher respiration rates and increased ATP turnover, and the export of osmolytes to maintain osmotic potential. As the duration of translational bursting is determined by cell-intrinsic factors, the period of oscillation is determined by the time cells take to store sufficient resources to license passage through the pH-dependent metabolic checkpoint that initiates translational bursting. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints have selected for temporal organisation that promotes oscillatory behaviour.

The protein phosphatase inhibitor okadaic acid induces defects in cytokinesis and organellar genome segregation in Trypanosoma brucei

1994 ◽  
Vol 107 (12) ◽  
pp. 3477-3483 ◽  
Author(s):  
A. Das ◽  
M. Gale ◽  
V. Carter ◽  
M. Parsons
Keyword(s):  
Cell Cycle ◽  
Mitochondrial Dna ◽  
Okadaic Acid ◽  
Protein Phosphatase ◽  
Specific Inhibitor ◽  
Eukaryotic Cell ◽  
Cell Cycles ◽  
African Trypanosomes ◽  
20 Nm

Mitosis and cytokinesis are events that are highly coordinated in most eukaryotic cell cycles. African trypanosomes possess a single mitochondrion and must additionally coordinate the organellar division cycle. Here we report that okadaic acid, a potent and specific inhibitor of protein phosphatases PP1and PP2A, uncouples these cycles in living trypanosomes. Cell cycle analysis of treated cells revealed elevated DNA content. Microscopic examination indicated that okadaic acid treatment yielded multinucleate cells with a single mitochondrial network indicating these cells have undergone mitosis but failed to complete cytokinesis. Immunofluorescence analysis of 5-bromo-2-deoxyuridine incorporation demonstrated that the mitochondrial DNA was replicated but did not segregate. The dose response curve for inhibition of the normal cell cycle paralleled that for the in vitro inhibition of protein phosphatase activities with IC50s of approximately 20 nM okadaic acid. These results suggest the involvement of a PP1/PP2A-like activity in coordinating mitosis, mitochondrial DNA division and cytokinesis in trypanosomes.

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