Is autophagy in response to ischemia and reperfusion protective or detrimental for the heart?

Sebastiano Sciarretta, Nirmala Hariharan, Yoshiya Monden, Daniela Zablocki, Junichi Sadoshima

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

Autophagy is a catabolic process that degrades long-lived proteins and damaged organelles by sequestering them into double membrane structures termed "autophagosomes" and fusing them with lysosomes. Autophagy is active in the heart at baseline and further stimulated under stress conditions including starvation, ischemia/reperfusion, and heart failure. It plays an adaptive role in the heart at baseline, thereby maintaining cardiac structure and function and inhibiting age-related cardiac abnormalities. Autophagy is activated by ischemia and nutrient starvation in the heart through Sirt1-FoxO- and adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent mechanisms, respectively. Activation of autophagy during ischemia is essential for cell survival and maintenance of cardiac function. Autophagy is strongly activated in the heart during reperfusion after ischemia. Activation of autophagy during reperfusion could be either protective or detrimental, depending on the experimental model. However, strong induction of autophagy accompanied by robust upregulation of Beclin1 could cause autophagic cell death, thereby proving to be detrimental. This review provides an overview regarding both protective and detrimental functions of autophagy in the heart and discusses possible applications of current knowledge to the treatment of heart disease.

Original languageEnglish (US)
Pages (from-to)275-281
Number of pages7
JournalPediatric Cardiology
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

Keywords

  • Autophagy
  • Beclin1
  • Ischemia/reperfusion

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Is autophagy in response to ischemia and reperfusion protective or detrimental for the heart?'. Together they form a unique fingerprint.

  • Cite this