The prefoldin ‐like protein AtURI exhibits characteristics of intrinsically disordered proteins
The prefoldin-like protein AtURI has a large, disordered region (colored red) at the C-terminus of the structured prefoldin domain (colored blue) that confers AtURI promiscuity for protein –protein interactions and instability to allow tight control of AtURI levels. The prefoldin-like protein UNCONVENTIONAL PREFOLDIN RPB5 INTERACTOR (URI) participates in diverse cellular functions, including protein homeostasis, transcription, translation, and signal transduction. Thus, URI is a highly versatile protein, although the molecular basis of this versatility remains unknown. In this work, we show thatArabidopsis thaliana (Arab...
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Yaiza G ómez‐Mínguez,
Alberto Palacios‐Abella,
Cecilia Costigliolo‐Rojas,
Mariana Barber,
Laura Hernández‐Villa,
Cristina Úrbez,
David Alabadí Tags: Research Article Source Type: research
Mdm2 ‐mediated ubiquitination of PKCβII is responsible for insulin‐induced heterologous desensitization of dopamine D3 receptor
In response to insulin stimulation, the E3 ligase enzyme Mdm2 exits the nucleus and interacts with PKC βII, facilitating the ubiquitination of PKCβII. Subsequently, the ubiquitinated PKCβII translocates to the cell membrane and associates with D3R, resulting in the inhibition of D3R cAMP signaling and linking it to clathrin-mediated endocytosis and degradation. The insulin and dopaminergic systems in the brain are associated with schizophrenia and Parkinson's disease with respect to etiology and treatment. The present study investigated the crosstalk between the insulin receptor (IR) and dopamine receptor and found that...
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Xingyue Zeng,
ChengYan Wu,
Yongkai Cao,
Huijun Li,
Xiaohan Zhang Tags: Research Article Source Type: research
Mitochondrial dysfunction in NPC1 ‐deficiency is not rescued by drugs targeting the glucosylceramidase GBA2 and the cholesterol‐binding proteins TSPO and StARD1
We examined two potential protein targets—translocator protein (TSPO) and steroidogenic acute regulatory protein D1 (StARD1)—which are implicated in cholesterol transport to mitochondria, in addition to glucocerbrosidase 2 (GBA2), the target of miglustat, which is currently the only approved treatment for NPCD. However, inhibiting these proteins did not correct the mitochondrial defect in NPC1-deficient cells. (Source: FEBS Letters)
Source: FEBS Letters - February 2, 2024 Category: Biochemistry Authors: Simon Wheeler,
Meenakshi Bhardwaj,
Victor Kenyon,
Maria J. Ferraz,
Johannes M. F. G. Aerts,
Dan J. Sillence Tags: Communication Source Type: research
Front Cover
Cover illustration The cover image refers to the article by Buechel and Pinkett ‘Activity of the pleiotropic drug resistance transcription factors Pdr1p and Pdr3p is modulated by binding site fl anking sequences’ (Source: FEBS Letters)
Source: FEBS Letters - January 29, 2024 Category: Biochemistry Tags: Issue Information Source Type: research
Dietary (poly)phenols as modulators of the biophysical properties in endothelial cell membranes: its impact on nitric oxide bioavailability in hypertension
Age is a risk factor to the onset and progression of hypertension, though adherence to plant-based diets improves blood pressure. Herein, we propose the potential of food (poly)phenols to fluidify cholesterol-rich endothelial membranes and improve the diffusion of nitric oxide (·NO) contributing to enhanced bioavailability of vascular·NO and the nutritional management of hypertension. Hypertension is a major contributor to premature death, owing to the associated increased risk of damage to the heart, brain and kidneys. Although hypertension is manageable by medication and lifestyle changes, the risk increases with age. ...
Source: FEBS Letters - January 29, 2024 Category: Biochemistry Authors: Ana Reis,
Barbara S. Rocha,
Jo ão Laranjinha,
Victor de Freitas Tags: Review Source Type: research
Lipid droplets and fatty acid ‐induced lipotoxicity: in a nutshell
Fatty acids (FAs) are critical molecules for cell growth, proliferation, and development; but are toxic to cells when present in excess. Eukaryotic cells therefore sequester FAs in organelles called lipid droplets (LDs) until needed. LD synthesis and breakdown are under precise metabolic control, and dysregulation of these pathways is linked to lipotoxicity and diseases. Lipid droplets (LDs) are fat storage organelles that are conserved from bacteria to humans. LDs are broken down to supply cells with fatty acids (FAs) that can be used as an energy source or membrane synthesis. An overload of FAs disrupts cellular function...
Source: FEBS Letters - January 29, 2024 Category: Biochemistry Authors: Eseiwi Obaseki,
Daniel Adebayo,
Sumit Bandyopadhyay,
Hanaa Hariri Tags: In a Nutshell Source Type: research
Autophagy ‐dependent alternative splicing of ribosomal protein S24 produces a more stable isoform that aids in hypoxic cell survival
Hypoxic human cells increase the abundance of a longer mRNA splice variant of ribosomal protein S24 (RPS24L) by retaining a 22 bp cassette exon. RPS24L is induced in an autophagy-dependent manner, while the shorter variant RPS24S is reduced by mTORC1 repression in a hypoxia-inducible factor-dependent manner. RPS24L produces a more stable protein isoform that aids in hypoxic cell survival. Cells remodel splicing and translation machineries to mount specialized gene expression responses to stress. Here, we show that hypoxic human cells in 2D and 3D culture models increase the relative abundance of a longer mRNA variant of...
Source: FEBS Letters - January 29, 2024 Category: Biochemistry Authors: Jenna Kerry,
Erin J. Specker,
Morgan Mizzoni,
Andrea Brumwell,
Leslie Fell,
Jenna Goodbrand,
Michael N. Rosen,
James Uniacke Tags: Research Article Source Type: research
Apolipoprotein E isoforms and their Cys ‐thiol modifications impact LRP1‐mediated metabolism of triglyceride‐rich lipoproteins
The current study offers a novel perspective on the physiological role of apolipoprotein (apo) E in lipid metabolism. The redox status of Cys-thiol in the apoE molecule significantly influences lipoprotein metabolismvia the low-density lipoprotein receptor-related protein (LRP) 1. Our findings are instrumental in understanding the pathology of various apoE-related diseases, including various atherosclerotic diseases and Alzheimer's disease. The low-density lipoprotein (LDL) receptor-related protein (LRP)1 participates in the metabolism of apolipoprotein (apo) E-containing lipoproteins (apoE-LP). We investigated the effects...
Source: FEBS Letters - January 27, 2024 Category: Biochemistry Authors: Hiroto Matsuura,
Shogo Akahane,
Takahiro Kaido,
Tomu Kamijo,
Kenta Sakamoto,
Kazuyoshi Yamauchi Tags: Research Article Source Type: research
Functional interplay of lipid droplets and mitochondria
Lipid droplets (LDs) make physical contacts with various organelles in eukaryotic cells including mitochondria. The existence of these contacts is well-known but poorly described. Here, we review recent advances in the understanding of the physical and functional links between LDs and mitochondria, and their implications in fatty acid transfer, cell signaling, and various diseases. Our body stores energy mostly in form of fatty acids (FAs) in lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes and mitochondria. This transfer is dependent on close opposition of LDs and mitochondria and p...
Source: FEBS Letters - January 25, 2024 Category: Biochemistry Authors: Ludovic Enkler,
Anne Spang Tags: Review Source Type: research
Uncovering mechanisms of interorganelle lipid transport by enzymatic mass tagging
Lipid transport is an essential process that underlies the biogenesis and expansion of organelles. Despite its basic importance, there is a dearth of assays to probe lipid exchange between organellesin vivo. Here we discuss the development of a versatile method called METALIC (Mass tagging-Enabled Tracking of Lipids in Cells), that uses enzyme-based mass tagging of lipids in conjunction with mass spectrometry to track interorganelle lipid transport inside living cells. Lipid trafficking is critical for the biogenesis and expansion of organelle membranes. Lipid transport proteins (LTPs) have been proposed to facilitate l...
Source: FEBS Letters - January 25, 2024 Category: Biochemistry Authors: Arun T. John Peter,
Benoit Kornmann Tags: In a Nutshell Source Type: research
