The heart of autophagy: Deconstructing cardiac proteotoxicity

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The heart is capable of robust structural remodeling, sometimes improving performance and sometimes leading to failure. Recent studies have uncovered a critical role for autophagy in disease-related remodeling of the cardiomyocyte. We have shown previously that hemodynamic load elicits a maladaptive autophagic response in cardiomyocytes which contributes to disease progression. In a recent study, we went on to demonstrate that protein aggregation is a proximal event triggering autophagic clearance mechanisms. The ubiquitin-proteasome-dependent pathways of protein clearance are similarly activated in parallel with processing of stress-induced protein aggregates into aggresomes and clearance through autophagy. These findings in the setting of pressure overload contrast with protein aggregation occurring in a model of protein chaperone malfunction in myocytes, where activation of autophagy is beneficial, antagonizing disease progression. Our findings situate heart disease stemming from environmental stress in the category of proteinopathy and raise important new questions regarding molecular events that elicit adaptive and maladaptive autophagy.

Original languageEnglish (US)
Pages (from-to)932-935
Number of pages4
JournalAutophagy
Volume4
Issue number7
StatePublished - Oct 1 2008

Fingerprint

Autophagy
Cardiac Myocytes
Disease Progression
Proteins
Proteasome Endopeptidase Complex
Ubiquitin
Heat-Shock Proteins
Muscle Cells
Heart Diseases
Hemodynamics
Pressure

Keywords

  • Cardiac hypertrophy
  • Cardiac remodeling
  • Cardiomyocyte
  • Heart failure

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

The heart of autophagy : Deconstructing cardiac proteotoxicity. / Rothermel, Beverly A; Hill, Joseph A.

In: Autophagy, Vol. 4, No. 7, 01.10.2008, p. 932-935.

Research output: Contribution to journalArticle

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