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Related Concept Videos

Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Smooth Endoplasmic Reticulum01:21

Smooth Endoplasmic Reticulum

Smooth endoplasmic reticulum or smooth ER is a sub-organelle with specialized functions in animal cells and plant cells. It is often associated with the tubule morphology of the endoplasmic reticulum.
The ER provides optimal conditions for synthesizing steroid hormones and lipids, such as phospholipids and triglycerides. Traditionally, lipid metabolism was considered to be a smooth ER function. However, there is no direct evidence to prove that rough ER is completely excluded from lipid...
The Endoplasmic Reticulum01:43

The Endoplasmic Reticulum

The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
The Endoplasmic Reticulum01:43

The Endoplasmic Reticulum

The endoplasmic reticulum or ER makes up for more than half of the membranes in a cell and accounts for 10% of total cell volume. It is also the primary protein and lipid synthesis factory for most cell organelles, such as the Golgi apparatus, lysosomes, secretory vesicles, and the plasma membrane. Despite being the most extensive and functionally complex subcellular organelle, ER was the last to be discovered. After years of deliberation, Keith Porter and George Palade in the year 1954,...
Assembly of the Lipid Bilayer in the ER01:28

Assembly of the Lipid Bilayer in the ER

Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
Endoplasmic Reticulum01:39

Endoplasmic Reticulum

Endoplasmic ReticulumThe endoplasmic reticulum (ER) is an extensive network of membranous sacs and tubules in eukaryotic cells, continuous with the outer membrane of the nucleus. This structural continuity integrates nuclear and cytoplasmic processes and facilitates efficient intracellular transport. This allows mRNA to move directly from the nucleus to ribosomes for efficient protein synthesis. As a result, the ER serves as a central site for the synthesis, processing, and distribution of...

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Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum
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Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum

Published on: January 22, 2019

Apical Proximal Tubule Fatty Acid Uptake-Generated Ceramides Cause Endoplasmic Reticulum Stress From Altered Membrane

Zhiyu Liu1, Robert J Gaivin1, Shenaz Khan1

  • 1Department of Physiology & Biophysics, Case Western Reserve University, Cleveland, United States of America.

JCI Insight
|June 18, 2026
PubMed
Summary

In chronic kidney disease, kidney cells reabsorb excess fatty acids (FA) via apical FATP2. This overwhelms lipid droplet formation, causing ceramide buildup and endoplasmic reticulum (ER) stress, leading to kidney cell damage.

Keywords:
Cell biologyChronic kidney diseaseNephrology

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Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
16:43

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

Published on: February 18, 2014

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Last Updated: Jun 20, 2026

Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum
07:49

Spontaneous Formation and Rearrangement of Artificial Lipid Nanotube Networks as a Bottom-Up Model for Endoplasmic Reticulum

Published on: January 22, 2019

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
16:43

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells

Published on: February 18, 2014

Area of Science:

  • Nephrology
  • Cell Biology
  • Biochemistry

Background:

  • Kidney proximal tubule cells normally reabsorb circulating fatty acids (FA) via basolateral transporters.
  • In chronic kidney disease, albumin-bound FA cross the damaged glomerular barrier and are reabsorbed by apical FA transport protein-2 (FATP2).
  • The roles of apical vs. basolateral FA uptake and intracellular mechanisms in kidney lipotoxicity remain unclear.

Purpose of the Study:

  • To investigate the contribution of apical versus basolateral fatty acid uptake to kidney proximal tubule cell lipotoxicity.
  • To elucidate the intracellular mechanisms underlying fatty acid-induced endoplasmic reticulum (ER) stress and cellular dysfunction.

Main Methods:

  • Incubation of human proximal tubule cells with palmitate (a fatty acid) via apical, basolateral, or both routes.
  • Analysis of endoplasmic reticulum (ER) stress markers, gene expression, and ER morphology.
  • Assessment of lipid droplet formation and ceramide levels.
  • Inhibition of lipid droplet formation and ceramide synthesis.

Main Results:

  • Apical or combined apical/basolateral palmitate exposure induced ER stress, ER fragmentation, and reduced lipid droplet formation.
  • Inhibition of lipid droplet formation exacerbated ER stress, indicating impaired FA metabolite sequestration.
  • Elevated C16:0 ceramide levels were observed, and ceramide synthesis inhibition ameliorated ER stress.
  • Transfection with C16:0 ceramide reduced ER membrane fluidity and induced ER stress.

Conclusions:

  • Aberrant apical reabsorption of FA by FATP2 in chronic kidney disease exceeds cellular lipid droplet incorporation capacity.
  • This leads to cytotoxicity driven by ceramide accumulation and subsequent endoplasmic reticulum (ER) lipid bilayer stress.