Biology subjects

Moren, B.

Publications and source records attributed to Moren, B..

3 recordsLinked to original sources

bioRxiv2025

Membrane contacts between caveolae and the endoplasmic reticulum regulate uptake and metabolic trapping of long-chain fatty acids

The vital process of cellular fatty acid metabolism involves uptake, metabolic trapping and storage of long-chain fatty acids (LCFAs) in different lipid species. Although several different enzymes like transporters and acyl-CoA synthetases are involved, the sequential mechanistic steps of the process are poorly understood. Here, we have addressed the role of the caveola coat protein caveolin1 and the acyl-CoA synthetase FATP1 in the process as both have major impacts in the uptake and storage of fatty acids in vivo and in vitro. Using live cell microscopy and mass spectrometry-based quantification of LCFA metabolism, we found that FATP1-mediated uptake and metabolic processing of LCFAs is coupled to, and dependent on caveolin1. Furthermore, both proteins stimulate the incorporation of LCFA into phospholipids and triacylglycerol, but not in sphingolipids. Using correlative light and electron microscopy we found that membrane contact sites are formed between FATP1-enriched endoplasmic reticulum (ER) and caveolae. Analysis of their temporal stability showed that they are dynamic but frequently persist over minutes. We propose that caveolae directly couple the plasma membrane (PM) to the ER for directed LCFA transport and metabolic processing.

cell biology↗

bioRxiv2025

Deep tissue optical 3D imaging reveals preferential preservation of extra-islet β-cells in late-onset Type 1 Diabetes

As residual {beta}-cell function may have positive effects on diabetes regulation in T1D, details on its spatial distribution and mass could provide important information for potential future therapeutic regimens. We implemented an optical 3D imaging pipeline to generate a first account of the 3D-spatial and volumetric distribution of the remaining {beta}-cells throughout the volume of an entire human late onset T1D pancreas at a microscopic resolution. As expected, {beta}-cell mass was dramatically lower than in the non-diabetic pancreas. However, the pancreatic head displayed a morphology and size resembling the non-diabetic pancreas and had a 3 times higher {beta}-cell density compared to the rest of the organ. Surprisingly, only a fraction of the residual {beta}-cells were located within islet structures. Instead, the absolute majority were present as extra-islet {beta}-cells, either as scattered individual cells or as clusters of {beta}-cells, spatially separated from all other endocrine cell-types. Jointly, these extra-islet {beta}-cells appeared roughly 60x less prone to succumb than islet associated {beta}-cells. In sharp contrast to {beta}-cell mass, -cell density appeared unaffected. This 3D whole organ depiction of an entire long standing, late onset, T1D pancreas shows that individual {beta}-cells may be preserved in a highly regionalized manner, potentially reflecting key aspects of disease dynamics.

pathology↗

bioRxiv2022

Dynamin2 stabilizes plasma membrane-connected caveolae by restraining fission

Caveolae are small membrane invaginations that generally are stably attached to the plasma membrane. Their release is believed to depend on the GTPase dynamin 2 (Dyn2), in analogy with its role in fission of clathrin-coated vesicles. The mechanistic understanding of caveola fission, and in particular the role of Dyn2, is however sparse. Here, we used microscopy-based tracking of individual caveolae in living cells to determine the role of Dyn2 in caveola dynamics. We report that Dyn2 stably associated with a subset of caveolae, but was not required for formation or fission of caveolae. The Dyn2-positive subset of caveolae displayed longer plasma membrane duration times, whereas depletion of Dyn2 resulted in shorter duration times and increased caveola fission. The stabilizing role of Dyn2 was independent of its GTPase activity and the caveola stabilizing protein EHD2. Thus, we propose that, in contrast to the current view, Dyn2 restrains caveolae at the plasma membrane and prevents fission.

cell biology↗