选择性自噬受体 SQSTM1/p62 以一种进化上保守的方式延长寿命和维持蛋白质稳态。
The selective autophagy receptor SQSTM1/p62 improves lifespan and proteostasis in an evolutionarily conserved manner.
机构信息
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Development, Aging and Regeneration Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
出版信息
Autophagy. 2020 Apr;16(4):772-774. doi: 10.1080/15548627.2020.1725404. Epub 2020 Feb 10.
The degradation of specific cargos such as ubiquitinated protein aggregates and dysfunctional mitochondria via macroautophagy/autophagy is facilitated by SQSTM1/p62, the first described selective autophagy receptor in metazoans. While the general process of autophagy plays crucial roles during aging, it remains unclear whether and how selective autophagy mediates effects on longevity and health. Two recent studies in the nematode and the fruit fly melanogaster observed gene expression changes of the respective SQSTM1 orthologs in response to environmental stressors or age and showed that overexpression of SQSTM1 is sufficient to extend lifespan and improve proteostasis and mitochondrial function in an autophagy-dependent manner in these model organisms. These findings show that increased expression of the selective autophagy receptor SQSTM1 is sufficient to induce aggrephagy in , and mitophagy in , and demonstrate an evolutionarily conserved role for SQSTM1 in lifespan determination.
通过巨自噬/自噬降解特定货物,如泛素化蛋白聚集体和功能失调的线粒体,这一过程由 SQSTM1/p62 介导,它是后生动物中第一个被描述的选择性自噬受体。虽然自噬的一般过程在衰老过程中起着至关重要的作用,但尚不清楚选择性自噬是否以及如何对长寿和健康产生影响。最近在秀丽隐杆线虫和黑腹果蝇中的两项研究观察到各自 SQSTM1 直系同源物的基因表达变化,以响应环境应激源或年龄,并表明 SQSTM1 的过表达足以延长寿命,并以自噬依赖的方式改善这些模式生物中的蛋白质稳态和线粒体功能。这些发现表明,选择性自噬受体 SQSTM1 的表达增加足以诱导 和 中的聚集自噬和线粒体自噬,并证明 SQSTM1 在寿命决定中的作用在进化上是保守的。
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