SIRT1–a new mammalian substrate of nuclear autophagy

Lu Wang, Caiyue Xu, Terje Johansen, Shelley L. Berger, Zhixun Dou

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Macroautophagic/autophagic degradation of nuclear components (or nuclear autophagy) is a poorly understood area in autophagy research. We previously reported the nuclear lamina protein LMNB1 (lamin B1) as a nuclear autophagy substrate in primary human cells, stimulating the investigation of nuclear autophagy in the mammalian system. We recently reported the sirtuin protein SIRT1 as a new selective substrate of nuclear autophagy in senescence and aging. Upon senescence of primary human cells, SIRT1 degradation is mediated by a direct nuclear SIRT1-LC3 interaction, followed by nucleus-to-cytoplasm shuttling of SIRT1 and autophagosome-lysosome degradation. In vivo, SIRT1 is downregulated by lysosomes in hematopoietic and immune organs upon natural aging in mice and in aged human T cells. Our study identified another substrate of nuclear autophagy and suggests a new strategy to promote SIRT1-mediated health benefits by suppressing its autophagic degradation. Abbreviations: HSPC: hematopoietic stem and progenitor cells; NAD+: nicotinamide adenine dinucleotide; SASP: senescence-associated secretory phenotype.

Original languageEnglish (US)
Pages (from-to)593-595
Number of pages3
JournalAutophagy
Volume17
Issue number2
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Aging
  • SIRT1
  • nuclear autophagy
  • senescence
  • sirtuin

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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