Related Experiment Video

Updated: Jun 24, 2025

Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy
07:05

Visualization of Neutrophil Extracellular Traps in Mesenteric Venules After Mesenteric Ischemia-Reperfusion Injury via Intravital Microscopy

Published on: September 27, 2024

438

ER-mitochondria association negatively affects wound healing by regulating NLRP3 activation

Caterina Licini1, Gianluca Morroni2, Guendalina Lucarini1

  • 1Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.

Cell Death & Disease
|June 11, 2024
PubMed

Insights

The antibiotic linezolid (LZD) hinders wound healing by increasing IL-1β in skin cells. This occurs through ER-mitochondria interactions that activate the NLRP3 inflammasome, a process that can be blocked to restore healing.

Area of Science:

  • Cell Biology
  • Immunology
  • Wound Healing Research

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA) causes significant skin infections globally.
  • Antibiotics like linezolid (LZD) are primary treatments but can impede wound repair.
  • Understanding antibiotic side effects on healing is crucial for patient outcomes.

Purpose of the Study:

  • To investigate the mechanism by which linezolid (LZD) impairs wound healing.
  • To identify molecular pathways linking LZD treatment to delayed skin repair.
  • To explore potential therapeutic targets for mitigating LZD-induced healing defects.

Main Methods:

  • Utilized keratinocyte models to study LZD effects on wound healing.
  • Investigated reactive oxygen species (ROS)-independent mitochondrial damage.
  • Analyzed endoplasmic reticulum (ER)-mitochondria interactions and NLRP3 inflammasome activation.
  • Assessed the impact of modulating ER-mitochondria contacts on IL-1β production and wound closure.

Main Results:

  • Linezolid (LZD) treatment increased interleukin 1β (IL-1β) production in keratinocytes, impairing wound healing.
  • LZD induced mitochondrial damage and enhanced ER-mitochondria tethering, independent of ROS.
  • This increased tethering promoted NLRP3 inflammasome assembly and activation.
  • Inhibiting ER-mitochondria contact formation restored normal wound closure by reducing IL-1β levels.

Conclusions:

  • Linezolid (LZD) disrupts wound healing by activating the NLRP3 inflammasome via ER-mitochondria crosstalk.
  • ER-mitochondria association is a critical regulator of NLRP3 inflammasome activation in this context.
  • Targeting ER-mitochondria interactions may offer a strategy to improve wound healing during LZD therapy.

More Related Videos

Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis06:36

Murine Excisional Wound Healing Model and Histological Morphometric Wound Analysis

Published on: August 21, 2020

12.2K
Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.09:06

Assessment of Acute Wound Healing using the Dorsal Subcutaneous Polyvinyl Alcohol Sponge Implantation and Excisional Tail Skin Wound Models.

Published on: March 25, 2020

8.7K

Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Phases of Wound Repair01:28

Phases of Wound Repair

Following injury, the integrity of the injured tissues must be reestablished. For example, in skin tissue, wound repair involves coordination among resident skin cells, blood mononuclear cells, extracellular matrix, growth factors, and cytokines to complete the healing cascade.
Formation of Blood Clot
In case of deep injuries, trauma to blood vessels results in blood loss. In the meantime, phospholipids released from the ruptured endothelial cellular membrane are converted into arachidonic...
6.0K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.5K
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K