Cellular Homeostasis and Quality Control

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Microenvironment".

Deadline for manuscript submissions: closed (31 July 2024) | Viewed by 1592

Special Issue Editors


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Guest Editor
Department of Biology, University of Fribourg, Chemin du Musée 10, CH-1700 Fribourg, Switzerland
Interests: membrane homeostasis; lipid droplet biogenesis; lipid transport; sterol export; CAP proteins; fatty acid transport

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Guest Editor
Denali Therapeutics, South San Francisco, CA, USA
Interests: mitochondrial dysfunction; lysosomal storage disorders; molecular chaperones; neurodegeneration; aging

Special Issue Information

Dear Colleagues,

The functioning of cells, as individual units or as components of complex tissue systems, rely on the maintenance of a steady and balanced physiological state. Such a state of homeostasis is enabled by a range of quality control mechanisms, responding to both internal as well as environmental changes that may disrupt optimal function. Cellular quality control ensures that subcellular components such as proteins are regulated at the level of synthesis, degradation as well as their precise localization. Similarly, cells regulate the uptake, synthesis and subcellular distribution of lipids and metabolites, allowing them to adapt to changing environments and respond to stress and damage. Achieving quality control also requires coordination between organelles performing diverse specialized functions. Thus, the maintenance of cellular homeostasis depends on a network of self-regulating feedback-controlled pathways and the failure of quality control mechanisms underlie numerous diseases afflicting millions of people worldwide. These include cancer, diabetes, and neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, to name a few.

We invite original research articles, reviews, as well as short perspective articles for a special issue on Cellular Homeostasis and Quality Control focusing on the following key areas:

  • Protein quality control: From chaperones to ubiquitin proteasome system to autophagy
  • Protein trafficking defects and human disease
  • Mitochondrial dysfunction and quality control
  • Lysosomal storage disorders
  • Cellular quality control and aging

In particular, submissions focusing on the failure of quality control pathways in relation to development and progression of human disease are particularly encouraged.

Prof. Dr. Roger Schneiter
Dr. Madhuja Samaddar
Guest Editors

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Keywords

  • cellular homeostasis
  • protein trafficking and quality control
  • mitochondrial dysfunction
  • lysosomal storage disorders
  • neurodegeration
  • aging

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Published Papers (1 paper)

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Research

20 pages, 4153 KiB  
Article
N-SREBP2 Provides a Mechanism for Dynamic Control of Cellular Cholesterol Homeostasis
by Tozen Ozkan-Nikitaras, Dominika J. Grzesik, Lisa E. L. Romano, J. P. Chapple, Peter J. King and Carol C. Shoulders
Cells 2024, 13(15), 1255; https://doi.org/10.3390/cells13151255 - 25 Jul 2024
Viewed by 881
Abstract
Cholesterol is required to maintain the functional integrity of cellular membrane systems and signalling pathways, but its supply must be closely and dynamically regulated because excess cholesterol is toxic. Sterol regulatory element-binding protein 2 (SREBP2) and the ER-resident protein HMG-CoA reductase (HMGCR) are [...] Read more.
Cholesterol is required to maintain the functional integrity of cellular membrane systems and signalling pathways, but its supply must be closely and dynamically regulated because excess cholesterol is toxic. Sterol regulatory element-binding protein 2 (SREBP2) and the ER-resident protein HMG-CoA reductase (HMGCR) are key regulators of cholesterol biosynthesis. Here, we assessed the mechanistic aspects of their regulation in hepatic cells. Unexpectedly, we found that the transcriptionally active fragment of SREBP2 (N-SREBP2) was produced constitutively. Moreover, in the absence of an exogenous cholesterol supply, nuclear N-SREBP2 became resistant to proteasome-mediated degradation. This resistance was paired with increased occupancy at the HMGCR promoter and HMGCR expression. Inhibiting nuclear N-SREBP2 degradation did not increase HMGCR RNA levels; this increase required cholesterol depletion. Our findings, combined with previous physiological and biophysical investigations, suggest a new model of SREBP2-mediated regulation of cholesterol biosynthesis in the organ that handles large and rapid fluctuations in the dietary supply of this key lipid. Specifically, in the nucleus, cholesterol and the ubiquitin–proteasome system provide a short-loop system that modulates the rate of cholesterol biosynthesis via regulation of nuclear N-SREBP2 turnover and HMGCR expression. Our findings have important implications for maintaining cellular cholesterol homeostasis and lowering blood cholesterol via the SREBP2-HMGCR axis. Full article
(This article belongs to the Special Issue Cellular Homeostasis and Quality Control)
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