Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts

Free Radic Biol Med. 2012 Nov 1;53(9):1760-9. doi: 10.1016/j.freeradbiomed.2012.08.591. Epub 2012 Sep 1.

Abstract

In the current literature, the lysosomal system is considered to be involved in the intracellular formation and accumulation of lipofuscin, a highly oxidized and covalently cross-linked aggregate of proteins that fills the lysosomal volume during aging. In contrast, our experimental results presented here suggest that both the autophagosomes and the lysosomal system are not mandatory for the formation of lipofuscin, since that material accumulates in the cytosolic volume if autophagy or lysosomal activity is inhibited. However, such an inhibition is accompanied by an enhanced toxicity of the formed protein aggregates. Furthermore, it could be proven that macroautophagy is responsible for the uptake of lipofuscin into the lysosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein 5
  • Cell Line
  • Cellular Senescence*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Fibroblasts / physiology
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Lipofuscin / metabolism*
  • Lysosome-Associated Membrane Glycoproteins / metabolism
  • Lysosomes / drug effects
  • Lysosomes / metabolism*
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Oxidative Stress*
  • Paraquat / pharmacology
  • Phagosomes / drug effects
  • RNA Interference
  • Reactive Oxygen Species / metabolism
  • Vacuolar Proton-Translocating ATPases / genetics
  • Vacuolar Proton-Translocating ATPases / metabolism

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • LAMP1 protein, human
  • Lipofuscin
  • Lysosome-Associated Membrane Glycoproteins
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • ATP6V0A1 protein, human
  • Vacuolar Proton-Translocating ATPases
  • Paraquat