Mitochondrial contribution to lipofuscin formation.
Mitochondria have been in the focus of oxidative stress and aging research for decades due to their permanent production of ROS during the oxidative phosphorylation. The hypothesis exists that mitochondria are involved in the formation of lipofuscin, an autofluorescent protein aggregate that accumulates progressively over time in lysosomes of post-mitotic and senescent cells. To investigate the influence and involvement of mitochondria in lipofuscinogenesis, we analyzed lipofuscin amounts as well as the mitochondrial function in young and senescent cells. In addition we used an aging model and Lon protease deficient HeLa cells to investigate the influence of mitochondrial degradation processes on lipofuscin formation. We were able to show that mitophagy is impaired in senescent cells resulting in an increased mitochondrial mass and superoxide formation. In addition, the inhibition of mitochondrial fission leads to increased lipofuscin formation. Moreover, we observed that Lon protease downregulation is linked to a higher lipofuscinogenesis whereas the application of the mitochondrial-targeted antioxidant mitoTEMPO is able to prevent the accumulation of this protein aggregate.
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany. Electronic address: jeannette.koenig@dife.de.
Jeannette
J
König
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany. Electronic address: christiane.ott@dife.de.
Christiane
C
Ott
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany. Electronic address: martin.hugo@dife.de.
Martín
M
Hugo
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Cardiovascular Research (DZHK), 10117 Berlin, Germany. Electronic address: tobias.jung@dife.de.
Tobias
T
Jung
Institut de Génomique Fonctionnelle de Lyon (IGFL) - ENS de Lyon, 69007 Lyon, France. Electronic address: anne-laure.bulteau@ens-lyon.fr.
Anne-Laure
AL
Bulteau
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany; German Center for Cardiovascular Research (DZHK), 10117 Berlin, Germany; NutriAct-Competence Cluster Nutrition Research Berlin-Potsdam, Nuthetal 14458, Germany. Electronic address: scientific.director@dife.de.
Tilman
T
Grune
Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany. Electronic address: annika.hoehn@dife.de.
Annika
A
Höhn
D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008062:Lipofuscin / Q000096:biosynthesis* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D063306:Mitophagy / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D049070:Protease La / Q000378:metabolism*; D066329:Protein Aggregates / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
D008062:Lipofuscin; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; D049070:Protease La
Aging; Lipofuscin; Lon protease; Mitochondria; Oxidative stress; Protein aggregates