title: Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts.
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.
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich Schiller University Jena, Germany. ahoehn@uni-hohenheim.de
authors.forename: Annika
authors.initials: A
authors.lastname: Höhn
authors.forename: Anna
authors.initials: A
authors.lastname: Sittig
authors.forename: Tobias
authors.initials: T
authors.lastname: Jung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Grimm
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
mesh_terms: D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D010588:Phagosomes / Q000187:drug effects; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D000071187:Autophagy-Related Protein 5; D008062:Lipofuscin; D051907:Lysosomal Membrane Proteins; D008869:Microtubule-Associated Proteins; D010269:Paraquat; D017382:Reactive Oxygen Species; D025262:Vacuolar Proton-Translocating ATPases; C502778:ATG5 protein, human; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C529316:ATP6V0A1 protein, human