The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity

Changhua Wang, Xuejun Wang

Research output: Contribution to journalReview article

40 Citations (Scopus)

Abstract

Proteotoxicity refers to the detrimental effects of damaged/misfolded proteins on the cell. Cardiac muscle is particularly susceptible to proteotoxicity because sustained and severe proteotoxic stress leads to cell death and the cardiac muscle has very limited self-renewal capacity. The ubiquitin-proteasome system (UPS) and the autophagic-lysosomal pathway (ALP) are two major pathways responsible for degradation of most cellular proteins. Alterations of UPS and ALP functions are associated with the accumulation of proteotoxic species in the heart, a key pathological feature of common forms of heart disease including idiopathic, ischemic, and pressure-overloaded cardiomyopathies and a large subset of congestive heart failure. Emerging evidence suggests that proteasome inhibition or impairment activates autophagy and conversely, acute ALP inhibition may sometimes increase intrinsic proteasome peptidase activities but chronic ALP inhibition hinders UPS performance in ubiquitinated protein degradation. The exact molecular basis on which the two degradative pathways interact remains largely undefined. Here we review current understanding of the roles of the UPS and autophagy in the control of cardiac proteotoxicity, with a specific focus on the crosstalk between the two pathways. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.

Original languageEnglish (US)
Pages (from-to)188-194
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1852
Issue number2
DOIs
StatePublished - Feb 1 2015

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Autophagy
Proteasome Endopeptidase Complex
Ubiquitin
Myocardium
Ubiquitinated Proteins
Proteins
Cardiomyopathies
Quality Control
Proteolysis
Heart Diseases
Peptide Hydrolases
Cell Death
Heart Failure
Pressure

Keywords

  • Autophagy
  • Heart disease
  • Proteotoxicity
  • Ubiquitin-proteasome system

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity. / Wang, Changhua; Wang, Xuejun.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1852, No. 2, 01.02.2015, p. 188-194.

Research output: Contribution to journalReview article

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