Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts

Kono, Keita; Johmura, Yoshikazu; Moriyama, Yoko; Masukagami, Yumiko; Nishimura, Koutarou; Barbee, H; Takase, Hiroshi; Sugiyama, Shinju; Sato, Yoshikatsu; Higashiyama, Tetsuya; Nakanishi, Makoto

doi:10.1101/2021.03.26.437120

Cited by 3 publications

(3 citation statements)

References 45 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We here introduced the diverse functions of protein phase transition upon membrane permeabilization. Membrane permeabilization and damage induces various biological processes, such as cytokine production and release, exosome secretion and cellular senescence ( 49 – 51 ) . The perspectives of protein phase transitions may provide better understandings of these processes associated with membrane permeabilization.…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic zoning by protein phase transition after membrane permeabilization

Sugiyama,

Suda,

Kono

2023

The Journal of Biochemistry

View full text Add to dashboard Cite

Summary Biological membranes, including plasma membrane (PM) and organelle membranes, restrict the flux of ions, molecules, and organelles. However, the barrier function of biological membranes is frequently compromised by various perturbations, including physical membrane damage and protein- or chemical-induced pore formation. Recent evidence suggests that, upon PM damage, protein gelation and solid condensation are utilized to restrict ion/molecule/organelle flux across the damaged membranes by zoning the cytoplasm. In addition, membrane permeabilization dramatically alters intramembrane and extramembrane ion/molecule concentrations via the flux across the permeabilized membrane. The changes in ion/molecule concentration and their downstream pathways induce protein phase transition to form zones for biological processes or protein sequestration. Here, we review the mechanisms and functions of protein phase transition after biological membrane permeabilization.

show abstract

Section: Discussionmentioning

confidence: 99%

Cytoplasmic zoning by protein phase transition after membrane permeabilization

Sugiyama,

Suda,

Kono

2023

The Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…In contrast to the mechanical techniques, the oscillation doesn't involve the deformation of plasma membrane, which may induce unexpected damage to the plasma membrane, leading to premature senescence or reduced cellular viability. [40] Moreover, mechanical oscillation could be easily applied in in vivo, which presents a challenge for techniques such as microinjection and microfluidics-based technologies.…”

Section: Synergistic Effect Of Lnps and Mechanical Oscillation On Mrn...mentioning

confidence: 99%

Enhancing Cytoplasmic Expression of Exogenous mRNA through Dynamic Mechanical Stimulation

Chen,

Patel,

Mir

et al. 2024

Preprint

View full text Add to dashboard Cite

Ionizable lipid nanoparticles (LNPs) have been pivotal in combating COVID-19, and numerous preclinical and clinical studies have highlighted their potential in nucleic acid-based therapies and vaccines. However, the effectiveness of endosomal escape for the nucleic acid cargos encapsulated in LNPs is still low, leading to suboptimal treatment outcomes and side effects. Hence, improving endosomal escape is crucial for enhancing the efficacy of nucleic acid delivery using LNPs. Here, a mechanical oscillation (frequency: 65 Hz) is utilized to prompt the LNP-mediated endosomal escape. The results reveal this mechanical oscillation can induce the combination and fusion between LNPs with opposite surface charges, enhance endosomal escape of mRNA by 14%, and increase the transfection efficiency of mRNA up to 1.67 times in the current study. Additionally, cell viability remains high at 99.3% after treatment with oscillation, which is comparable to that of untreated cells. Furthermore, there is no obvious damage to other membranous organelles. Thus, this work presents a user-friendly and safe approach to enhancing endosomal escape of mRNA and boosting gene expression. As a result, our work can be potentially utilized in both research and clinical fields to facilitate LNP-based delivery by enabling more effective release of LNP-encapsulated cargos from endosomes.

show abstract

“…The specific composition of lipids within membranes dictates their biophysical properties such as diffusion, permeability, domain formation, and curvature generation. Age-related changes in membrane lipid composition have been postulated to be one of the hallmarks of aging [1][2][3] .…”

Section: Introductionmentioning

confidence: 99%

Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline

Gao,

Tom,

Rydz

et al. 2024

Preprint

View full text Add to dashboard Cite

The retina is uniquely enriched in polyunsaturated fatty acids (PUFAs), which are primarily localized in cell membranes, where they govern membrane biophysical properties such as diffusion, permeability, domain formation, and curvature generation. During aging, alterations in lipid metabolism lead to reduced content of very long-chain PUFAs (VLC-PUFAs) in the retina, and this decline is associated with normal age-related visual decline and pathological age-related macular degeneration (AMD).ELOVL2(Elongation of very-long-chain fatty acids-like 2) encodes a transmembrane protein that produces precursors to docosahexaenoic acid (DHA) and VLC-PUFAs, and methylation level of its promoter is currently the best predictor of chronological age. Here, we show that mice lacking ELOVL2-specific enzymatic activity (Elovl2C234W) have impaired contrast sensitivity and slower rod response recovery following bright light exposure. Intravitreal supplementation with the direct product of ELOVL2, 24:5n-3, in aged animals significantly improved visual function and reduced accumulation of ApoE, HTRA1 and complement proteins in sub-RPE deposits. At the molecular level, the gene expression pattern observed in retinas supplemented with 24:5n-3 exhibited a partial rejuvenation profile, including decreased expression of aging-related genes and a transcriptomic signature of younger retina. Finally, we present the first human genetic data showing significant association of several variants in the humanELOVL2locus with the onset of intermediate AMD, underlying the translational significance of our findings. In sum, our study identifies novel therapeutic opportunities and defines ELOVL2 as a promising target for interventions aimed at preventing age-related vision loss.

show abstract

Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts

Cited by 3 publications

References 45 publications

Cytoplasmic zoning by protein phase transition after membrane permeabilization

Cytoplasmic zoning by protein phase transition after membrane permeabilization

Enhancing Cytoplasmic Expression of Exogenous mRNA through Dynamic Mechanical Stimulation

Polyunsaturated Fatty Acid - mediated Cellular Rejuvenation for Reversing Age-related Vision Decline

Contact Info

Product

Resources

About