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Published on: July 21, 2023
Macroautophagy and Chaperone-Mediated Autophagy in Heart Failure: The Known and the Unknown
Rajeshwary Ghosh1, J Scott Pattison1
1Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, Vermillion, SD, USA.
Insights
Autophagy, a cellular cleaning process, plays a critical role in heart health by removing damaged components. Understanding its complex roles in cardiac diseases may unlock new therapeutic strategies.
Area of Science:
- Cardiovascular Biology and Disease
- Cellular Biology
- Molecular Medicine
Background:
- Cardiac diseases are increasingly linked to the accumulation of misfolded proteins and damaged organelles.
- Autophagy, a key protein degradation pathway, is vital for cellular homeostasis and clearing cellular damage.
Purpose of the Study:
- To review the major types of autophagic processes (macroautophagy, chaperone-mediated autophagy, selective mitophagy) and their regulation in cardiac physiology and pathology.
- To discuss genetic models, markers, and methods for studying autophagy in the heart.
- To summarize current research on autophagy's dual role in cardiac pathology and its therapeutic potential.
Main Methods:
- Comprehensive literature review of autophagic processes, their regulation, and roles in cardiac disease.
- Analysis of genetic models for studying autophagy.
- Discussion of methods and markers for assessing autophagic activity in cardiac tissues.
Main Results:
- Autophagy encompasses macroautophagy, chaperone-mediated autophagy, and selective mitophagy, each with distinct structures and functions.
- Studies show conflicting results regarding macroautophagy's role, suggesting both cardioprotective and detrimental effects in heart failure.
- Autophagy markers and measurement methods are crucial for interpreting its activity in cardiac pathology.
Conclusions:
- Autophagy plays a significant and complex role in cardiac health and disease.
- Further understanding of autophagy regulation is essential for developing novel therapeutic interventions for cardiac conditions.
- Targeting autophagy pathways may offer a new therapeutic avenue for treating heart diseases.
Abstract:
Cardiac diseases including hypertrophic and ischemic cardiomyopathies are increasingly being reported to accumulate misfolded proteins and damaged organelles. These findings have led to an increasing interest in protein degradation pathways, like autophagy, which are essential not only for normal protein turnover but also in the removal of misfolded and damaged proteins. Emerging evidence suggests a previously unprecedented role for autophagic processes in cardiac physiology and pathology. This review focuses on the major types of autophagic processes, the genes and protein complexes involved, and their regulation. It discusses the key similarities and differences between macroautophagy, chaperone-mediated autophagy, and selective mitophagy structures and functions. The genetic models available to study loss and gain of macroautophagy, mitophagy, and CMA are discussed. It defines the markers of autophagic processes, methods for measuring autophagic activities, and their interpretations. This review then summarizes the major studies of autophagy in the heart and their contribution to cardiac pathology. Some reports suggest macroautophagy imparts cardioprotection from heart failure pathology. Meanwhile, other studies find macroautophagy activation may be detrimental in cardiac pathology. An improved understanding of autophagic processes and their regulation may lead to a new genre of treatments for cardiac diseases.
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