Myocardial ischemia-reperfusion injury: The balance mechanism between mitophagy and NLRP3 inflammasome

Life Sci. 2024 Oct 15:355:122998. doi: 10.1016/j.lfs.2024.122998. Epub 2024 Aug 20.

Abstract

Myocardial ischemia-reperfusion injury (MIRI) is an injury to cardiomyocytes due to restoration of blood flow after myocardial infarction (MI). It has recently gained much attention in clinical research with special emphasis on the roles of mitochondrial autophagy and inflammation. A mild inflammatory response promotes recovery of post-ischemic cardiomyocyte function and vascular regeneration, but a severe inflammatory response can cause irreversible and substantial cellular damage. Similarly, moderate mitochondrial autophagy can help inhibit excessive inflammation and protect cardiomyocytes. However, MIRI is aggravated when mitochondrial function is disrupted, such as inadequate clearance of damaged mitochondria or excessive activation of mitophagy. How to moderately control mitochondrial autophagy while promoting its balance with nucleotide-binding oligomerization structural domain receptor protein 3 (NLRP3) inflammasome activation is critical. In this paper, we reviewed the molecular mechanisms of mitochondrial autophagy and NLRP3 inflammasome, described the interaction between NLRP3 inflammasome and mitochondrial autophagy, and the effects of different signaling pathways and molecular proteins on MIRI, to provide a reference for future research.

Keywords: Inflammatory response; Mitochondrial autophagy; Myocardial ischemia-reperfusion injury; Nucleotide-binding oligomerization structural domain receptor protein 3; Signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammasomes* / metabolism
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitophagy*
  • Myocardial Reperfusion Injury* / metabolism
  • Myocardial Reperfusion Injury* / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Signal Transduction

Substances

  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Inflammasomes