Skip to Content
You are currently on the new version of our website. Access the old version .

Cells

Cells is an international, peer-reviewed, open access journal on cell biology, molecular biology, and biophysics, published semimonthly online by MDPI.
The Nordic Autophagy Society (NAS), the Spanish Society of Hematology and Hemotherapy (SEHH) and the International Cell Death Society (ICDS) are affiliated with Cells and their members receive discounts on the article processing charges.
Indexed in PubMed | Quartile Ranking JCR - Q2 (Cell Biology)

All Articles (20,074)

Inherited retinal degenerations, such as retinitis pigmentosa, are a leading cause of irreversible vision loss, yet broadly effective treatments remain elusive. Impaired cellular waste clearance via autophagy–lysosomal pathways have been implicated in photoreceptor death, but the spatiotemporal dynamics of these processes during degeneration remain poorly understood. Using the rd10 mouse model of retinitis pigmentosa, we characterised autophagy–lysosomal dysfunction at key stages of photoreceptor degeneration (postnatal day P17, P22, P35) through super-resolution imaging of RFP-EGFP-LC3 reporter mice, Western blot, and bulk RNA sequencing. Autophagosome and autolysosome numbers were significantly elevated across all photoreceptor compartments (inner/outer segments, outer nuclear layer, outer plexiform layer) at P17, prior to significant photoreceptor nuclei loss. Autophagosome and autolysosome size progressively increased from P22 onwards, suggesting accumulation of unprocessed intracellular waste. Molecular analyses revealed downregulation of mTOR protein, upregulation of autophagy-related genes, and increased lysosomal processes from P17. These histological and molecular findings are consistent with early autophagy induction followed by overwhelmed degradative capacity. Our findings identify autophagy–lysosomal change as an early event in photoreceptor loss in the rd10 model, revealing a critical therapeutic window for mutation-independent interventions targeting cellular clearance pathways in inherited retinal degenerations.

13 February 2026

Histological analysis of retina from WT and rd10 mice during development shows loss of the photoreceptors in the outer nuclear layer (ONL) of rd10 mice by postnatal day 22. Representative images of central transverse retina from WT at (A) P17, (B) P22, and (C) P35 in comparison to rd10 at (D) P17, (E) P22 and (F) 35 labelled for cell nuclei using (Bisbenzimide, blue) and imaged using confocal microscopy. (G) Quantitative analysis of ONL area per length of central retina shows that at P17, the thickness of ONL is similar between WT and rd10. At P22 and P35 there is significant loss of ONL in rd10 mice relative to age matched WT controls (p < 0.01). Data are expressed as mean ± SEM for n = 6 mice at each age. Data were analysed using a two-way ANOVA and post hoc between WT and rd10 with significance shown, n = 6, ** p < 0.01.

Fluorescence Intensity of Protein Tags Is Dependent on Their Subcellular Location

  • Yan Chen,
  • John P. Eichorst and
  • Joseph P. Albanesi
  • + 2 authors

Fluorescent protein (FP) tagging is widely used in imaging experiments to investigate the subcellular distribution of proteins. However, because the fluorescence of most FP chromophores is quenched upon their protonation, their fluorescence intensities are dependent on their pKas and on the environmental pH. Thus, the concentration of a protein tagged with EGFP (pKa = 6.0) is dramatically underestimated in the lysosomal lumen (pH ~4.7) compared to that of the same protein tagged with mCherry (pKa = 4.5). In this study, we examined the effect of differential FP tagging on the apparent subcellular distribution of several proteins that reside on the cytoplasmic surfaces of secretory/endocytic organelles. Due to the presumed uniformity of cytoplasmic conditions (pH ~7.2–7.4), we expected to find essentially complete overlap of fluorescent signals, regardless of the nature of the fused FP. However, we were surprised to observe significant discrepancies in the apparent distributions of a subset of proteins tagged with EGFP vs. mCherry (Pearson’s correlation coefficients of about 0.80). These discrepancies were not evident when comparing proteins tagged with mCherry vs. other FPs with low pKas (e.g., mTurquoise (pKa = 4.5), mCerulean (pKa = 3.2)) (Pearson’s correlation coefficients of about 0.90–0.95). Our results suggest that FP tags may be sensitive to the microenvironments on the cytoplasmic surfaces of different organelles.

13 February 2026

Co-expression of EGFP-PI4K2A and mCherry-PI4K2A in U2OS cells. Epifluorescence images are shown together with the color bar representing the camera counts for each imaged color. The right-side panel is an overlay of both color images. Pearson’s correlation coefficients (PCCs) of EGFP and mCherry signals were 0.84 ((top) panels) and 0.72 ((bottom) panels). Scale bars = 10 μm.

Immune checkpoint inhibitors have transformed the treatment landscape for advanced melanoma in the past 15 years, delivering unprecedented and durable survival benefits. This success has propelled the development of complementary immune-directed therapies, including cancer vaccines. Among these, synthetic long peptide (SLP) and mRNA vaccine platforms have emerged as highly promising. Advances in next-generation sequencing technology, alongside computational neoantigen algorithm predictions, have enabled patient-specific neoantigen identification to improve vaccine immunogenicity and enhance therapeutic efficacy. Off-the-shelf and personalised SLP and mRNA vaccines have demonstrated the ability to induce robust antigen-specific T-cell responses and modulate the tumour microenvironment. Mechanistically, cancer vaccines synergise with immune checkpoint inhibition. This review outlines the current clinical development of mRNA and peptide vaccines in melanoma, highlighting the significant promise to synergise with immune checkpoint inhibition to enhance efficacy without adding to the systemic toxicity profile. The neoadjuvant setting, characterised by intact tumour antigens and draining lymphatic architecture, offers a compelling biological context for leveraging cancer vaccines for enhanced immune priming and response assessment. Collectively, the rapid advances in technology and emerging clinical data position cancer vaccines as a promising therapy capable of improving immunotherapy in Stage III and IV melanoma.

13 February 2026

Diagrammatic representation of the mRNA and SLP vaccine manufacturing process. Figure created using Biorender®.

Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson’s disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations—G2019S in the kinase domain and I1371V in the GTPase domain—across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies.

13 February 2026

Differential effect of LRRK2 genetic variants, G2019S and I1371V, on membrane cholesterol and membrane fluidity. (A,C) Quantification of membrane cholesterol content in WT, LRRK2-G2019S (GS), and LRRK2-I1371V (IV) transfected SH-SY5Y (A) (N = 5 biological replicates) and U87 (C) cells (N = 6 biological replicates), measured by cholesterol ELISA of isolated membrane fractions. (B,D) Quantification of total cellular cholesterol content in WT, GS, and IV transfected SH-SY5Y (B) (N = 5 biological replicates) and U87 (D) cells (N = 6 biological replicates). (E–G) Membrane anisotropy measurements in WT, GS, and IV transfected SH-SY5Y (E), U87 (F), and floor plate cells (FPCs) (G), determined by fluorescence polarization spectroscopy using a TMA-DPH fluoroprobe (N = 5 biological replicates). Data is represented as the mean ± SD. ^: ANOVA comparison of WT vs. IV/GS; #: GS vs. IV. Single symbol: p  <  0.05; double symbol: p < 0.01; triple symbol: p  <  0.001.

News & Conferences

Issues

Open for Submission

Editor's Choice

Reprints of Collections

Inflammation
Reprint

Inflammation

The Cause of all Diseases 2.0
Editors: Vasso Apostolopoulos, Jack Feehan, Vivek P. Chavda
Cellular and Molecular Mechanisms in Immune Regulation
Reprint

Cellular and Molecular Mechanisms in Immune Regulation

Editors: Fábio Rinaldo Santori, Natalia B. Ivanova

Get Alerted

Add your email address to receive forthcoming issues of this journal.

XFacebookLinkedIn
Cells - ISSN 2073-4409