SIRT1 – a new mammalian substrate of nuclear autophagy
- 20 December 2020
- journal article
- research article
- Published by Taylor & Francis Ltd in Autophagy
- Vol. 17 (2), 593-595
- https://doi.org/10.1080/15548627.2020.1860541
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.Keywords
Funding Information
- NIH (grant K99AG065500)
- Glenn/AFAR Scholarship for Research in the Biology of Aging from American Federation of Aging Research
- TOPPFORSK (grant number 249884)
- Research Council of Norway
- NIH (grant P01AG031862)
- NIH (grant R00AG053406 and R35GM137889)
- Glenn Foundation for Medical Research
- AFAR (Grant for Junior Faculty)
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