Related Experiment Video

Updated: Jul 3, 2026

In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
08:35

In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells

Published on: June 12, 2017

Autophagy is an adaptive response in desmin-related cardiomyopathy

Paul Tannous1, Hongxin Zhu, Janet L Johnstone

  • 1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Proceedings of the National Academy of Sciences of the United States of America
|July 16, 2008
PubMed

Insights

Autophagy increases in desmin-related cardiomyopathy (DRCM) due to alphaB-crystallin mutations. This autophagic activity is adaptive, as inhibiting it worsens heart failure and protein aggregate accumulation.

Area of Science:

  • Cardiovascular Biology
  • Molecular Biology
  • Cellular Biology

Background:

  • Desmin-related cardiomyopathy (DRCM) is a severe heart condition caused by mutations in the alphaB-crystallin (CryAB) gene.
  • DRCM is characterized by the accumulation of misfolded proteins and aggregates within cardiomyocytes.
  • The role of cellular stress responses, such as autophagy, in DRCM pathogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of autophagy in response to protein aggregates in DRCM.
  • To determine if autophagic activity is an adaptive or detrimental response in this proteotoxic cardiomyopathy.

Main Methods:

  • Utilized a mouse model with cardiomyocyte-restricted overexpression of mutant alphaB-crystallin (CryAB(R120G)).
  • Assessed autophagic activity and protein aggregate levels in cardiomyocytes.
  • Examined the impact of blunting autophagy (using beclin 1 heterozygous inactivation) on disease progression and cardiac function.

Main Results:

  • Mutant CryAB(R120G) significantly increased cardiomyocyte autophagic activity.
  • Inhibition of autophagy led to increased aggregate accumulation, interstitial fibrosis, and accelerated cardiac dysfunction.
  • Early and robust autophagic activity was detected in CryAB(R120G) mice before significant cardiac decline.

Conclusions:

  • Autophagy is activated in response to proteotoxic stress in desmin-related cardiomyopathy.
  • Autophagic activation serves as an adaptive mechanism to mitigate the accumulation of misfolded proteins and slow disease progression.
  • Targeting or enhancing autophagy may represent a therapeutic strategy for DRCM.

More Related Videos

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice08:40

In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice

Published on: November 22, 2017

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome07:56

Visualizing Mitophagy with Fluorescent Dyes for Mitochondria and Lysosome

Published on: November 30, 2022

Related Concept Videos

Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Cardiomyopathy V: Interprofessional Care01:29

Cardiomyopathy V: Interprofessional Care

Managing cardiomyopathy involves addressing underlying or precipitating causes, treating heart failure with medications, and implementing dietary changes and a balanced exercise and rest regimen.Lifestyle ModificationsCardiomyopathy patients should adopt a low-sodium diet to reduce fluid retention and manage heart failure. A personalized exercise and rest plan helps maintain physical fitness without overstraining the heart. Avoiding alcohol and tobacco is essential to prevent further damage to...
Cardiomyopathy III: Hypertrophic Cardiomyopathy01:29

Cardiomyopathy III: Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy, or HCM, is an autosomal dominant genetic disorder characterized by asymmetric left ventricular hypertrophy without ventricular dilation. It is more common in men and is typically diagnosed in young, athletic adults.EtiologyHCM is primarily genetic and is caused by mutations in genes encoding sarcomeric proteins. Researchers have identified over 1400 mutations across at least 11 different genes. Among these, the most frequently occurring mutations are found in the...