Lipid droplets, autophagy, and ER stress as key (survival) pathways during ischemia-reperfusion of transplanted grafts

Cell Biol Int. 2024 Mar;48(3):253-279. doi: 10.1002/cbin.12114. Epub 2024 Jan 4.

Abstract

Ischemia-reperfusion injury is an event concerning any organ under a procedure of transplantation. The early result of ischemia is hypoxia, which causes malfunction of mitochondria and decrease in cellular ATP. This leads to disruption of cellular metabolism. Reperfusion also results in cell damage due to reoxygenation and increased production of reactive oxygen species, and later by induced inflammation. In damaged and hypoxic cells, the endoplasmic reticulum (ER) stress pathway is activated by increased amount of damaged or misfolded proteins, accumulation of free fatty acids and other lipids due to inability of their oxidation (lipotoxicity). ER stress is an adaptive response and a survival pathway, however, its prolonged activity eventually lead to induction of apoptosis. Sustaining cell functionality in stress conditions is a great challenge for transplant surgeons as it is crucial for maintaining a desired level of graft vitality. Pathways counteracting negative consequences of ischemia-reperfusion are autophagy and lipid droplets (LD) metabolism. Autophagy remove damaged organelles and molecules driving them to lysosomes, digested simpler compounds are energy source for the cell. Mitophagy and ER-phagy results in improvement of cell energetic balance and alleviation of ER stress. This is important in sustaining metabolic homeostasis and thus cell survival. LD metabolism is connected with autophagy as LD are degraded by lipophagy, a source of free fatty acids and glycerol-thus autophagy and LD can readily remove lipotoxic compounds in the cell. In conclusion, monitoring and pharmaceutic regulation of those pathways during transplantation procedure might result in increased/improved vitality of transplanted organ.

Keywords: ER stress; IRI; MAMs; autophagy; lipid droplets; transplantation.

Publication types

  • Review

MeSH terms

  • Autophagy
  • Endoplasmic Reticulum Stress
  • Fatty Acids, Nonesterified* / metabolism
  • Humans
  • Hypoxia / metabolism
  • Ischemia / metabolism
  • Lipid Droplets* / metabolism
  • Reperfusion

Substances

  • Fatty Acids, Nonesterified