Related Experiment Video

Updated: Jun 9, 2026

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes
08:56

Modeling Mitochondrial Disease Using Brain Organoids: A Focus on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes

Published on: October 10, 2025

Disruption of endothelial tight junctions in a patient with mitochondrial encephalomyopathy, lactic acidosis and

M Matsuzaki1, R Takahashi, T Nakayama

  • 1Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. mi.matsu@ped.twmu.ac.jp

Neuropediatrics
|August 28, 2010
PubMed

Insights

Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) involves disrupted capillary tight junctions, potentially causing edema and acidosis. This finding offers new insights into MELAS pathology.

Area of Science:

  • Neurology
  • Mitochondrial Diseases
  • Cell Biology

Background:

  • Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a severe maternally inherited disorder.
  • The A3243G mitochondrial DNA (mtDNA) point mutation is a common cause of MELAS.
  • The precise pathological mechanisms underlying MELAS, particularly endothelial dysfunction, remain incompletely understood.

Observation:

  • Electron microscopy was used to examine muscle and brain tissue from a patient with MELAS and the A3243G mtDNA mutation.
  • Tissue samples were obtained at different ages (5 years 1 month for muscle, 13 years 6 months for brain).

Findings:

  • The study revealed significant disruption of capillary endothelial tight junctions (TJs) in both muscle and brain tissues.
  • This disruption was observed in a patient with MELAS and the specific A3243G mtDNA mutation.

Implications:

  • Endothelial barrier disruption in MELAS may lead to vasogenic edema and systemic lactic acidosis.
  • These findings suggest that compromised endothelial TJs could be a critical pathological feature of MELAS.
  • Understanding this mechanism may open new avenues for therapeutic interventions in MELAS patients.

More Related Videos

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells06:15

Evaluation of Bioenergetic Function in Cerebral Vascular Endothelial Cells

Published on: November 19, 2016

Generation of Human Brain Organoids for Mitochondrial Disease Modeling08:09

Generation of Human Brain Organoids for Mitochondrial Disease Modeling

Published on: June 21, 2021

Related Concept Videos

Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
The Inner Mitochondrial Membrane01:28

The Inner Mitochondrial Membrane

The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Hepatic Encephalopathy01:29

Hepatic Encephalopathy

DefinitionHepatic encephalopathy is a reversible neurologic syndrome that results from advanced liver dysfunction or portosystemic shunting. It leads to disturbances in cognition, behavior, and motor function due to the brain’s exposure to gut-derived toxins that the liver fails to detoxify.EtiologyThis condition develops either in the setting of acute fulminant hepatitis or progressively during chronic liver disease, such as cirrhosis and portal hypertension. Portosystemic shunting—including...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...