Single-nucleus multi-omic profiling of polyploid heart nuclei identifies fusion-derived cardiomyocytes in the human heart. DOI Creative Commons
Sangita Choudhury,

Indu Sivankutty,

Youngsook L. Jung

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 30, 2024

Abstract Understanding the mechanisms of polyploidization in cardiomyocytes is crucial for advancing strategies to stimulate myocardial regeneration. Although endoreplication has long been considered primary source polyploid human cardiomyocytes, recent animal work suggests potential cardiomyocyte fusion. Moreover, effects on genomic-transcriptomic repertoire have not studied previously. We applied single-nuclei whole genome sequencing, single nuclei RNA and multiome ATAC + gene expression (from same nuclei) techniques isolated from 11 healthy hearts. Utilizing post-zygotic non-inherited somatic mutations occurring during development as “endogenous barcodes,” reconstruct lineage relationships cardiomyocytes. Of 482 multiple donor hearts 75.7% can be sorted into several developmental clades marked by one or more single-nucleotide variants (SNVs). At least ~10% tetraploid contain cells distinct clades, indicating fusion lineally cells, whereas 60% higher-ploidy fused clades. Combined snRNA-seq snATAC-seq revealed transcriptome chromatin landscapes diploid show some with transcriptional signatures suggesting between endothelial fibroblast cells. These observations provide first evidence cell nuclear raising possibility that may contribute developing maintaining heart.

Language: Английский

Mechanically operated signalling scaffolds DOI Creative Commons
Neil J. Ball, Samuel F. H. Barnett, Benjamin T. Goult

et al.

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 517 - 527

Published: April 4, 2024

Cellular signalling is a complex process and involves cascades of enzymes that, in response to specific signal, give rise exact cellular responses. Signalling scaffold proteins organise components these pathways space time co-ordinate outputs. In this review we introduce new class mechanically operated scaffolds that are built into the cytoskeletal architecture cell. These contain force-dependent binary switch domains integrate chemical mechanical signals quantised positional changes ligands persistent alterations providing mechanomemory capabilities. We focus on concept spatial organisation, how cell organises molecules at plasma membrane create order distinct The dynamic positioning using switches adds an additional layer complexity idea scaffolding. can spatiotemporally substrates dynamically, with introduction ∼50 nm steps distance between them as patterns change. Together different types engaging them, provide way for ordering extends beyond current views

Language: Английский

Citations

3
Lipid-anchored proteasomes control membrane protein homeostasis DOI Creative Commons
Ruizhu Zhang, S Pan,

Suya Zheng

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(48)

Published: Nov. 29, 2023

Protein degradation in eukaryotic cells is mainly carried out by the 26S proteasome, a macromolecular complex not only present cytosol and nucleus but also associated with various membranes. How proteasomes are anchored to membrane biological meaning thereof have been largely unknown higher organisms. Here, we show that N-myristoylation of Rpt2 subunit general mechanism for proteasome-membrane interaction. Loss this modification Rpt2-G2A mutant leads profound changes membrane-associated proteome, perturbs endomembrane system, undermines critical cellular processes such as cell adhesion, endoplasmic reticulum-associated protein trafficking. Rpt2G2A/G2A homozygous mutation embryonic lethal mice sufficient abolish tumor growth nude xenograft model. These findings defined an evolutionarily conserved maintaining homeostasis underscored significance compartmentalized myristoyl-anchored health disease.

Language: Английский

Citations

7
Membrane Epilipidome—Lipid Modifications, Their Dynamics, and Functional Significance DOI
Sider Penkov, Maria Fedorova

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(7), P. a041417 - a041417

Published: Jan. 22, 2024

Lipids are characterized by extremely high structural diversity translated into a wide range of physicochemical properties. As such, lipids vital for many different functions including organization cellular and organelle membranes, control organismal energy metabolism, as well mediating multiple signaling pathways. To maintain the lipid chemical to achieve rapid remodeling required responsiveness adaptability living systems make use network modifications already existing that complement rather slow biosynthetic Similarly biopolymers, which can be modified epigenetically posttranscriptionally (for nucleic acids) or posttranslationally proteins), also undergo alterations through oxygenation, nitration, phosphorylation, glycosylation, etc. In this way, an expanded collective we term "epilipidome," provides ultimate level complexity biological membranes delivers battery active small-molecule compounds numerous regulatory processes. tightly controlled often occur in response extra- intracellular stimuli at defined locations, emergence epilipidome greatly contributes spatial temporal compartmentalization diverse Accordingly, epilipid observed all organisms among most consistent prerequisites complex life.

Language: Английский

Citations

2
Faa1 membrane binding drives positive feedback in autophagosome biogenesis via fatty acid activation DOI Creative Commons
Verena Baumann, Sonja Achleitner, Susanna Tulli

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(7)

Published: April 4, 2024

Autophagy serves as a stress response pathway by mediating the degradation of cellular material within lysosomes. In autophagy, this is encapsulated in double-membrane vesicles termed autophagosomes, which form from precursors referred to phagophores. Phagophores grow lipid influx endoplasmic reticulum into Atg9-positive compartments and local synthesis provides lipids for their expansion. How phagophore nucleation expansion are coordinated with unclear. Here, we show that Faa1, an enzyme activating fatty acids, recruited Atg9 directly binding negatively charged membranes preference phosphoinositides such PI3P PI4P. We define membrane-binding surface Faa1 its direct interaction membrane required recruitment Furthermore, physiological localization key efficient catalysis promotes Our results suggest positive feedback loop coupling synthesis.

Language: Английский

Citations

2
Surfaces as frameworks for intracellular organization DOI
Germán Rivas, Allen P. Minton

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(11), P. 942 - 954

Published: Oct. 7, 2024

Language: Английский

Citations

2
Lipids: plant biology’s slippery superheroes DOI Creative Commons
Hortense Moreau, Emmanuelle Bayer

Frontiers in Plant Physiology, Journal Year: 2023, Volume and Issue: 1

Published: Oct. 23, 2023

Lipids are not only structural elements that make up biological membranes, they also play a crucial role in functionalizing these membranes. Through their ability to modulate membrane physical properties, act as sensors and signaling molecules, interact with proteins influence subcellular localization activity, lipids contribute the intricate workings of plant cells. The enrichment specific within distinct compartments aids establishment membranes unique identity properties. major regulators many cellular processes including cell signaling, division, polarity, trafficking, intra- intercellular communication, growth, responses environmental stress. In fact, immense diversity lipid species provides cells an extensive arsenal tools establish distinctive biochemical identities this review, we present overview lipids, emphasizing stress response by highlighting recent advancements field.

Language: Английский

Citations

6
Simplified Equilibrium Model for Exploring the Combined Influences of Concentration, Aggregate Shape, Excluded Volume, and Surface Adsorption upon Aggregation Propensity and Distribution of Globular Macromolecules DOI
Allen P. Minton

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(43), P. 9303 - 9311

Published: Oct. 23, 2023

A mesoscopic model for the equilibrium self-association of a globular macromolecule that may form oligomers various shapes and unlimited sizes is presented. Allowance made within this effects variation in free energy subunit contact an oligomer specified size different shapes, adsorption shape to planar surface, nonspecific excluded volume interaction between inert species occupying fraction total volume. The analytically soluble permits rapid calculation analysis each three parameters upon concentration dependence weight-average stoichiometry oligomer, adsorbed, differently shaped are adsorbed solution.

Language: Английский

Citations

4
A molecular container providing supramolecular protection against acetylcholine hydrolysis DOI

Yilong Lu,

Jing Su, Jianwei Li

et al.

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(8), P. 1634 - 1638

Published: Jan. 1, 2024

Utilizing confinement effects, TBTQ-C6 safeguards acetylcholine and butyrylcholine from enzymatic breakdown by AChE BChE through host–guest interactions.

Language: Английский

Citations

1
Ribosome External Electric Field Regulates Metabolic Enzyme Activity: The RAMBO Effect DOI Creative Commons
Jian-Chao Yu,

Lisa Ramirez,

Qishan Lin

et al.

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Ribosomes bind to many metabolic enzymes and change their activity. A general mechanism for ribosome-mediated amplification of enzyme activity, RAMBO, was formulated elucidated the glycolytic triosephosphate isomerase, TPI. The RAMBO effect results from a ribosome-dependent electric field-substrate dipole interaction energy that can increase or decrease ground state reactant product regulate catalytic rates. NMR spectroscopy used determine surface TPI binding ribosomes measure corresponding kinetic rates in absence presence intact ribosome particles. Chemical cross-linking mass spectrometry revealed potential ribosomal protein partners Structural related changes energetics activity show between L11 mediate effect.

Language: Английский

Citations

1
Pck2 association with the plasma membrane and efficient response of the cell integrity pathway require regulation of PI4P homeostasis by exomer DOI Creative Commons
Esteban Moscoso‐Romero, Sandra Moro,

Alicia Duque

et al.

Open Biology, Journal Year: 2024, Volume and Issue: 14(11)

Published: Nov. 1, 2024

Exomer is a protein complex that facilitates trafficking between the Golgi and plasma membrane (PM). Schizosaccharomyces pombe exomer composed of Cfr1 Bch1, we have found full activation cell integrity pathway (CIP) in response to osmotic stress requires exomer. In wild-type, CIP activators Rgf1 (Rho1 GEF) Pck2 (PKC homologue) MEK kinase Mkh1 localize PM, internalize after shock re-localize adaptation. This re-localization inefficient mutants. Overexpression PM-associated 1-phosphatidylinositol 4-kinase stt4+ , deletion nem1+ phosphatase suppress defects dynamics mutants, but not their defect activation, demonstrating regulates additional ways. mutants accumulate PI4P TGN, increasing expression Golgi-associated pik1+ suppresses dynamics. These findings suggest efficient transport from PM Mutants lacking clathrin adaptors are defective or accumulation Golgi. Hence, traffic participates this regulation through an exclusive mechanism.

Language: Английский

Citations

1