Mammalian nucleophagy: process and function

The nucleus is a highly specialized organelle that houses the cell's genetic material and regulates key cellular activities, including growth, metabolism, protein synthesis, and cell division. Its structure and function are tightly regulated by multiple mechanisms to ensure cellular integrity and genomic stability. Increasing evidence suggests that nucleophagy, a selective form of autophagy that targets nuclear components, plays a critical role in preserving nuclear integrity by clearing dysfunctional nuclear materials such as nuclear proteins (lamins, SIRT1, and histones), DNA-protein crosslinks, micronuclei, and chromatin fragments. Impaired nucleophagy has been implicated in aging and various pathological conditions, including cancer, neurodegeneration, autoimmune disorders, and neurological injury. In this review, we focus on nucleophagy in mammalian cells, discussing its mechanisms, regulation, and cargo selection, as well as evaluating its therapeutic potential in promoting human health and mitigating disease.