Abstract
The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. Here, we show that ageing elicits a marked increase of SUMO levels in C. elegans. In turn, SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. SUMOylation of DAF-16 modulates mitochondrial homeostasis by interfering with mitochondrial dynamics and mitophagy. Our findings reveal that SUMO is an important determinant of lifespan, and provide novel insight, relevant to the complexity of the signalling mechanisms that influence gene expression to govern organismal survival in metazoans.
Highlights
The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors
We find that the amount of small ubiquitin like modifier (SUMO) conjugated proteins peaks at day 4 of adulthood in C. elegans (Fig. 1A)
Considering, that HSF-1 has been shown to have the potential to be modified by SUMO, both in m ammals[48] and in C. elegans[49], we focused our studies on SKN-1 and DAF-16
Summary
The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. DAF-16 and SKN-1 are key regulators of these two processes[10] The activity of these transcription factors is modulated by many targeted posttranslational protein modifications, including phosphorylation, methylation, and ubiquitination[11,12,13]. SUMOylation, the attachment of a small ubiquitin like modifier (SUMO) to a target protein, is a posttranslational modification that plays pivotal roles in fundamental cellular processes including DNA damage responses, Scientific Reports | (2020) 10:15513. A causative relationship between SUMOylation and ageing has not been established
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