Lipofuscin-bound iron is a major intracellular source of oxidants: role in senescent cells

Free Radical Biology & Medicine
Annika HöhnTilman Grune

Abstract

Aging is accompanied by an intracellular accumulation of lipofuscin, a hydrophobic yellow-brownish material that accumulates especially in the lysosomal compartment, where it can be neither degraded nor exocytosed from the cell. The intracellular effects of accumulating lipofuscin are still a subject of speculation. In addition to the demonstrated inhibition of the proteasome, it was proposed that lipofuscin is cytotoxic because of its ability to incorporate transition metals such as copper and iron, resulting in a redox-active surface, able to catalyze the Fenton reaction. This characteristic of lipofuscin may contribute to an increased level of radical formation and oxidatively modified cellular components such as proteins, lipids, and RNA/DNA, which has been shown to be extensive in aging cells. In this study for the first time the lipofuscin-mediated formation of oxidants and the role of iron in this process are directly shown in a model of senescent fibroblasts, as well as in vitro with artificial lipofuscin. We demonstrate that this oxidant production is independent of mitochondria and has cytotoxic effects. The ability of lipofuscin to produce oxidants is dependent on the amount of transition metals incorporated. Althoug...Continue Reading

Citations

Jun 18, 2010·Amino Acids·S GrimmT Grune
Apr 12, 2013·Age·Emmanuelle BoilanOlivier Toussaint
Oct 16, 2010·Photochemistry and Photobiology·Sarah D LamoreGeorg T Wondrak
Jan 22, 2013·Journal of Proteomics·Annika HöhnTilman Grune
May 21, 2013·Journal of Proteomics·José Pedro CastroHenrique Almeida
Sep 15, 2010·Free Radical Research·Anne Negre-SalvayreNeven Zarkovic
Oct 23, 2010·Free Radical Research·Irena Szumiel
Jun 1, 2014·Experimental Gerontology·Kerstin NowotnyAnnika Höhn
Oct 14, 2014·Experimental Gerontology·Kerstin NowotnyAnnika Höhn
Oct 31, 2012·Molecular Aspects of Medicine·Niki ChondrogianniEfstathios S Gonos
Aug 21, 2010·Journal of Photochemistry and Photobiology. B, Biology·Sarah D LamoreGeorg T Wondrak
Jan 8, 2011·The Biochemical Journal·Rachael A DunlopKenneth J Rodgers
Oct 8, 2011·Journal of Neuroscience Methods·Kelsey A PotterJeffrey R Capadona
Sep 3, 2014·Antioxidants & Redox Signaling·Sandra Reeg, Tilman Grune
Dec 21, 2010·Free Radical Biology & Medicine·Annika HöhnTilman Grune
Mar 19, 2014·Free Radical Biology & Medicine·Annika HöhnTilman Grune
Sep 12, 2013·Redox Biology·Annika Höhn, Tilman Grune
Aug 21, 2013·Mechanisms of Ageing and Development·Anastasia PiyanovaAndras Bilkei-Gorzo
Apr 30, 2016·Ageing Research Reviews·Didac Carmona-GutierrezChristoph Ruckenstuhl
Sep 24, 2016·Archives of Pharmacal Research·Jung-Hwan Kang, Se-Young Choung
Oct 13, 2016·Scientific Reports·Grasiella Angelina AndrianiCristina Montagna
Oct 27, 2016·Biochimica Et Biophysica Acta. General Subjects·Waleska K MartinsMaurício S Baptista
Feb 20, 2014·Metallomics : Integrated Biometal Science·Douglas B Kell, Etheresia Pretorius
Jul 12, 2018·The Journal of Pharmacy and Pharmacology·Yong Seong KimDong Seok Cha
Aug 19, 2018·The European Journal of Neuroscience·Enrico Bagnoli, Una FitzGerald
Apr 30, 2014·The Journal of Biological Chemistry·Rabea AslehAndrew P Levy
Jan 4, 2020·Cellular and Molecular Life Sciences : CMLS·Janusz Blasiak
Jul 22, 2018·Frontiers in Neuroscience·Alexandra Moreno-GarcíaMiguel Calero
Jul 13, 2019·Frontiers in Aging Neuroscience·Carolina OsorioAdonis Sfera
Feb 25, 2020·Oxidative Medicine and Cellular Longevity·Alexandra BarboutiPanagiotis Kanavaros
May 8, 2014·Metallomics : Integrated Biometal Science·Alexandra GrubmanKatja M Kanninen
May 8, 2018·Analytical Cellular Pathology (Amsterdam)·Ulises UrzuaNicole Hernandez
Apr 24, 2018·Oxidative Medicine and Cellular Longevity·M PajaresM Cahova
Jan 11, 2019·International Journal of Molecular Sciences·Janusz BlasiakKai Kaarniranta
Mar 3, 2019·Scientific Reports·Yu KakimotoMotoki Osawa
Mar 20, 2020·Oxidative Medicine and Cellular Longevity·Perinur BozaykutBetul Karademir Yilmaz
Aug 4, 2019·Biogerontology·Sudhakar Krittika, Pankaj Yadav

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.