Nucleophagy in Human Disease: Beyond the Physiological Role (Retracted article. See vol. 244, pg. 175, 2018)

摘要

Autophagy is an evolutionarily conserved intracellular strategy for degrading organelles and proteins, and nucleophagy refers to the specific process of removing nuclear components from cells by autophagy, Nucleophagy is essential for cell survival by maintaining normal nuclear structure and functions. On the other hand, excessive nucleophagy may result in degradation of essential nuclear components, while impaired nucleophagy may lead to accumulation of harmful metabolic products in the nucleus. Therefore, dysregulation of nucleophagy is likely involved in the pathological process of certain diseases, including psoriasis, cancer, metabolic disorders and aging-related diseases. Nucleophagy is achieved with the participation of various proteins, including proteins encoded by autophagy-related genes (Atg), such as Atg39 and Atg40, as well as nuclear lamina protein lamin B1 and microtubule-associated protein 1 light chain 3 (LC3). Lamin B1 and LC3 are located in the nucleus. Moreover, there are different autophagy patterns in nucleophagy, such as piecemeal microautophagy, late nucleophagy, and micronuclei. Among them, micronuclei are considered a special form of nucleophagy detected in mammalian cells, referring to chromosomes or chromosome fragments that are enclosed by nuclear membrane. The presence of micronuclei usually indicates genotoxic events or the instability of chromosomes. However, in contrast to the well characterized cytoplasmic autophagy, our knowledge on nucleophagy is limited. Here we overview the potential involvement of nucleophagy in human diseases and then summarize the molecular events in the process of nucleophagy.