Autophagy and the ubiquitin-proteasome system in cardiac dysfunction

Q. Zheng, X. Wang

Research output: Contribution to journalReview article

34 Scopus citations

Abstract

The ubiquitin-proteasome system (UPS) and autophagy are two major intracellular protein degradation pathways. The UPS mediates the removal of soluble abnormal proteins as well as the targeted degradation of most normal proteins that are no longer needed. Autophagy is generally responsible for bulky removal of defective organdies and for sequestering portions of cytoplasm for lysosomal degradation during starvation. Impaired or inadequate protein degradation in the heart is associated with and may be a major pathogenic factor for a wide variety of cardiac dysfunctions, while enhanced protein degradation is also implicated in the development of cardiac pathology. It was generally assumed that the UPS and autophagy serve distinct functions. Therefore, the functional roles of the UPS and autophagy lathe hearts have been largely investigated separately. However, recent advances in understanding the shared mechanisms contributing to UPS alteration and the induction of autophagy have helped reveal the link and interplay between the two proteolytic systems in the heart. These links are exemplified by scenarios in which inadequate UPS proteolytic function leads to activation of autophagy, helping alleviate proteotoxic stress. It Is becoming increasingly clear that a coordinated and complementary relationship between the two systems is critical to protect cells against stress. Several proteins including p62, NDR1, HDAC6, and co-chaperones appear to play an important role in harmonizing and mobilizing the consortium formed by the UPS and autophagy.

Original languageEnglish (US)
Pages (from-to)9-25
Number of pages17
JournalPanminerva Medica
Volume52
Issue number1
StatePublished - Mar 2010

Keywords

  • Autophagy
  • Cytoprotection
  • Heart diseases

ASJC Scopus subject areas

  • Medicine(all)

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