Related Experiment Video

Updated: May 9, 2025

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)
06:44

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Published on: January 10, 2025

383

Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in

Seiji Watanabe1, Koji Yamanaka1,2,3,4,5

  • 1Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, Japan.

Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology
|May 5, 2025
PubMed

Insights

The mitochondria-endoplasmic reticulum contact site (MAM) is crucial for cell health but is disrupted in neurodegenerative diseases like ALS. Therapies targeting MAM offer future prospects for treating these conditions.

Area of Science:

  • Cellular Biology
  • Neuroscience
  • Biochemistry

Background:

  • The mitochondria-endoplasmic reticulum (ER) contact site, known as the mitochondria-associated membrane (MAM), is vital for cellular homeostasis.
  • MAM regulates key cellular processes including calcium transfer, lipid synthesis, mitochondrial dynamics, and autophagy.

Purpose of the Study:

  • To review the disruption of protein homeostasis in neurodegenerative diseases.
  • To present recent findings on the mechanisms of MAM aberration, with a focus on amyotrophic lateral sclerosis (ALS).
  • To discuss future therapeutic strategies targeting MAM for neurodegenerative diseases.

Main Methods:

  • Literature review of protein homeostasis disruption in neurodegenerative diseases.
  • Analysis of recent research on MAM aberration mechanisms.
  • Focus on specific research related to ALS and MAM.

Main Results:

  • MAM protein accumulation is linked to disrupted cellular functions.
  • Aberrations in MAM are implicated in neurodegenerative conditions like ALS and Alzheimer's disease.
  • Specific mechanisms of MAM dysfunction in ALS have been investigated.

Conclusions:

  • MAM plays a critical role in cellular homeostasis and its disruption contributes to neurodegeneration.
  • Understanding MAM aberration mechanisms is key to developing targeted therapies.
  • Future research should focus on developing MAM-targeted therapies for neurodegenerative diseases.
Keywords:
mitochondria‐associated membranesneurodegenerative diseasesprotein homeostasis

More Related Videos

Author Spotlight: Regulation and Dysregulation of ER-Mitochondria Contacts — Implications for Neurodegenerative Disease Pathogenesis09:09

Author Spotlight: Regulation and Dysregulation of ER-Mitochondria Contacts — Implications for Neurodegenerative Disease Pathogenesis

Published on: October 11, 2024

1.4K
Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells09:34

Study of Endoplasmic Reticulum and Mitochondria Interactions by In Situ Proximity Ligation Assay in Fixed Cells

Published on: December 10, 2016

24.5K

Related Concept Videos

Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.0K
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...
3.3K
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...
2.3K
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...
4.9K
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...
4.3K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.6K