Nucleophagy: The guardian of genome stability - from molecular mechanisms to disease associations.

作者：Lei Chen, Fen Feng, Qun Zhou, Lin-Xi Chen · 发表于：Life Science · 年份：2026 · DOI：10.1016/j.lfs.2026.124270 · 研究领域：Medicine

Nucleophagy is a crucial process by which cells selectively degrade nuclear components through autophagy mechanisms to maintain genomic stability. It occurs through two modes: macro-nucleophagy and micro-nucleophagy, relying on proteins such as Atg39 and Nvj1 to remove irreversibly damaged nuclear components (such as broken chromatin, micronuclei, and abnormal nuclear membrane components) caused by irreversible DNA damage, to degrade toxic nuclear protein aggregates, and to target abnormal nuclear structural components. The activity of nucleophagy is regulated at multiple levels. Transcription factors such as the MiT/TFE family and p53 can sense cellular stress signals to regulate the expression of autophagy genes. Epigenetic mechanisms such as DNA methylation, histone modification, and miRNA participate in the regulation by modifying genes or marking substrates, and these regulatory processes are modulated by signaling molecules and drugs such as mTOR inhibitors. The core function of nucleophagy is to eliminate irreparable damaged nuclear substances, toxic nuclear protein aggregates, and abnormal nuclear structural components, thereby preventing the accumulation of harmful substances. It also exerts a bidirectional regulatory role in pathological processes including cell differentiation, aging, cardiovascular diseases, neurodegenerative diseases, and cancer. Future research needs to further elucidate the regulatory mechanisms of nucleophagy, particularly the crosstalk betwee...