Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Autophagy. 2021 Feb;17(2):593-595. doi: 10.1080/15548627.2020.1860541. Epub 2020 Dec 20.
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. HSPC: hematopoietic stem and progenitor cells; NAD: nicotinamide adenine dinucleotide; SASP: senescence-associated secretory phenotype.
核成分的巨自噬/自噬降解（或核自噬）是自噬研究中一个尚未被充分了解的领域。我们之前曾报道核层蛋白 LMNB1（核纤层蛋白 B1）是人原代细胞中核自噬的底物，这激发了对哺乳动物系统中核自噬的研究。我们最近报道了去乙酰化酶 SIRT1 是衰老和老化过程中核自噬的一种新的选择性底物。在人原代细胞衰老过程中，SIRT1 的降解是通过核 SIRT1-LC3 的直接相互作用介导的，随后 SIRT1 发生核质穿梭，被自噬体-溶酶体降解。在体内，随着小鼠自然衰老和人 T 细胞衰老，溶酶体下调造血和免疫器官中的 SIRT1。我们的研究鉴定了核自噬的另一种底物，并提出了一种通过抑制其自噬降解来促进 SIRT1 介导的健康益处的新策略。HSPC：造血干细胞和祖细胞；NAD：烟酰胺腺嘌呤二核苷酸；SASP：衰老相关分泌表型。
