Asymmetric Inheritance of Oxidatively Damaged Proteins During Cytokinesis

Aguilaniu, Hugo; Gustafsson, Lena; Rigoulet, Michel; Nyström, Thomas

doi:10.1126/science.1080418

Cited by 592 publications

(569 citation statements)

References 15 publications

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“…All protein samples were resolved by electrophoresis through 10% gradient SDS‐polyacrylamide gel. Proteins were detected by immunoblot using the OxyBlot Protein Oxidation Detection Kit following the provided protocol (Aguilaniu, Gustafsson, Rigoulet, & Nyström, 2003). Detections were accomplished using the ECL Plus Western Blotting Detection System following the provided instructions.…”

Section: Methodsmentioning

confidence: 99%

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response

et al. 2018

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Plant extracts containing salicylates are probably the most ancient remedies to reduce fever and ease aches of all kind. Recently, it has been shown that salicylates activate adenosine monophosphate‐activated kinase (AMPK), which is now considered as a promising target to slow down aging and prevent age‐related diseases in humans. Beneficial effects of AMPK activation on lifespan have been discovered in the model organism Caenorhabditis elegans (C. elegans). Indeed, salicylic acid and acetylsalicylic acid extend lifespan in worms by activating AMPK and the forkhead transcription factor DAF‐16/FOXO. Here, we investigated whether another salicylic acid derivative 5‐octanoyl salicylic acid (C8‐SA), developed as a controlled skin exfoliating ingredient, had similar properties using C. elegans as a model. We show that C8‐SA increases lifespan of C. elegans and that a variety of pathways and genes are required for C8‐SA‐mediated lifespan extension. C8‐SA activates AMPK and inhibits TOR both in nematodes and in primary human keratinocytes. We also show that C8‐SA can induce both autophagy and the mitochondrial unfolded protein response (UPRmit) in nematodes. This induction of both processes is fully required for lifespan extension in the worm. In addition, we found that the activation of autophagy by C8‐SA fails to occur in worms with compromised UPRmit, suggesting a mechanistic link between these two processes. Mutants that are defective in the mitochondrial unfolded protein response exhibit constitutive high autophagy levels. Taken together, these data therefore suggest that C8‐SA positively impacts longevity in worms through induction of autophagy and the UPRmit.

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Section: Methodsmentioning

confidence: 99%

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response

et al. 2018

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“…In addition oxidative modification does not affect the proteome uniformly, in that some proteins are more prevalent targets (Cabiscol et al, 2000). In studies of budding yeast, carbonylated proteins were visualized in single cells and seen to accumulate with increased replicative age (Aguilaniu et al, 2003). Thus protein modifications due to oxidative damage may alter the balance of functional repair proteins present at a DSB and ultimately affect the changes to the broken chromosome after repair.…”

Section: Discussionmentioning

confidence: 99%

Does age influence loss of heterozygosity?

Carr

Gottschling

2008

Experimental Gerontology

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The striking correlation between advanced age and an increased incidence of cancer has led investigators to examine the influence of aging on genome maintenance.Because loss of heterozygosity (LOH) can lead to the inactivation of tumor suppressor genes, and thus carcinogenesis, understanding the affect of aging on this type of mutation event is particularly important. Several factors may affect the rate of LOH, including an increase in the amount of DNA damage, specifically double-strand breaks (DSB), and the ability to efficiently repair this damage via pathways that minimize the loss of genetic information. Because of experimental constraints, there is only suggestive evidence for a change in the rate of DNA damage as humans age. However, recent studies in model organisms find that there are increased rates of LOH with age, and that repair of DNA damage occurs via a different pathway in old cells versus young cells. We speculate that the age-dependent change in DNA repair may explain why there is increased LOH, and that the findings from these model organisms may extend to humans.

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“…Additional evidence for SQC comes from experiments demonstrating that oxidatively damaged (carbonylated) proteins do not diffuse freely but are controlled in space such that one cell is kept essentially free of damaged proteins during the process of cytokinesis [19]. This asymmetrical inheritance of damage was revealed using budding yeast as a model system for replicative ageing and follow-up experiments demonstrated that (i) oxidatively damaged proteins coalesce into aggregates recognized by the protein remodelling factor Hsp104p [20], (ii) Hsp104p-containing aggregates become tethered to the actin cables rather than the microtubule [21], and (iii) aggregates tethered to the cables do not enter the progeny because the flow of the actin cables is away from the daughter cell bud tip [21].…”

Section: Spatial Quality Control and Its Links To Ageingmentioning

confidence: 99%

Spatial protein quality control and the evolution of lineage-specific ageing

Nyström

2011

Phil. Trans. R. Soc. B

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Propagation of a species requires periodic cell renewal to avoid clonal extinction. Sexual reproduction and the separation of germ cells from the soma provide a mechanism for such renewal, but are accompanied by an apparently mandatory ageing of the soma. Data obtained during the last decade suggest that a division of labour exists also between cells of vegetatively reproducing unicellular organisms, leading to the establishment of a soma-like and germ-like lineage with distinct fitness and longevity characteristics. This division of labour in both bacteria and yeast entails segregation of damaged and aggregated proteins such that the germ-like lineage is kept free of damage to the detriment of the soma-like lineage. In yeast, this spatial protein quality control (SQC) encompasses a CCT-chaperonin-dependent translocation and merging of cytotoxic protein aggregates. This process is regulated by Sir2, a protein deacetylase that modulates the rate of ageing in organisms ranging from yeast to worms and flies. Recent data also demonstrate that SQC is intimately integrated with the machinery establishing proper cell polarity and that this machinery is required for generating a soma-like and germ-like lineage in yeast. Deciphering the details of the SQC network may increase our understanding of the development of age-related protein folding disorders and shed light on the selective forces that paved the way for polarity and lineage-specific ageing to evolve.

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Asymmetric Inheritance of Oxidatively Damaged Proteins During Cytokinesis

Cited by 592 publications

References 15 publications

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response

A salicylic acid derivative extends the lifespan of Caenorhabditis elegans by activating autophagy and the mitochondrial unfolded protein response

Does age influence loss of heterozygosity?

Spatial protein quality control and the evolution of lineage-specific ageing

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