RRC ID 44052
Author Höhn A, Sittig A, Jung T, Grimm S, Grune T.
Title Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts.
Journal Free Radic Biol Med
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.
Volume 53(9)
Pages 1760-9
Published 2012-11-1
DOI 10.1016/j.freeradbiomed.2012.08.591
PII S0891-5849(12)01108-2
PMID 22982048
MeSH 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
IF 6.17
Times Cited 36
Human and Animal Cells Atg5^(+/+)MEF(RCB2710) Atg5^(-/-)MEF(RCB2711)