Nucleophagy—Implications for Microautophagy and Health

Abstract

Nucleophagy, the selective subtype of autophagy that targets nuclear material for autophagic degradation, was not only shown to be a model system for the study of selective macroautophagy, but also for elucidating the role of the core autophagic machinery within microautophagy. Nucleophagy also emerged as a system associated with a variety of disease conditions including cancer, neurodegeneration and ageing. Nucleophagic processes are part of natural cell development, but also act as a response to various stress conditions. Upon releasing small portions of nuclear material, micronuclei, the autophagic machinery transfers these micronuclei to the vacuole for subsequent degradation. Despite sharing many cargos and requiring the core autophagic machinery, recent investigations revealed the aspects that set macro- and micronucleophagy apart. Central to the discrepancies found between macro- and micronucleophagy is the nucleus vacuole junction, a large membrane contact site formed between nucleus and vacuole. Exclusion of nuclear pore complexes from the junction and its exclusive degradation by micronucleophagy reveal compositional differences in cargo. Regarding their shared reliance on the core autophagic machinery, micronucleophagy does not involve normal autophagosome biogenesis observed for macronucleophagy, but instead maintains a unique role in overall microautophagy, with the autophagic machinery accumulating at the neck of budding vesicles.

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Protects the Growth and Survival of Cancer Cells

“…Mammalian cells have a nuclear lamina structure, which is different from that of lower eukaryotes, such as yeasts, with no comparable lamins or a fibrous nuclear envelope scaffold ( 29 ). Nevertheless, nucleophagy is considered to play an important role in maintaining cellular genomic stability, detecting DNA damage, and regulating cellular apoptosis, as well as cellular senescence ( 30 , 31 ). MN assays showed increased MN frequencies in breast cancer lymphocytes, which were correlated with the progression of breast cancer ( 32 ).…”

Autophagy-Mediated Clearance of Free Genomic DNA in the Cytoplasm Promoted the Growth and Survival of Breast Cancer Cells

“…Mammalian cells have a nuclear lamina structure, which is different from that of lower eukaryotes, such as yeasts, with no comparable lamins or a brous nuclear envelope scaffold [23]. Nevertheless, nucleophagy is considered to play an important role in maintaining cellular genomic stability, detecting DNA damage, and regulating cellular apoptosis, as well as cellular senescence [24,25]. MN assays showed increased MN frequencies in breast cancer lymphocytes, which were correlated with the progression of breast cancer [26].…”

Regulation of Lipid Metabolism by Lamin in Mutation-Related Diseases

“…Nuclear autophagy, a new type of selective autophagy, is responsible for selectively removing damaged or unnecessary nuclear substances in cells (Fu et al, 2018). Nuclear autophagy happens in a variety of conditions, including starvation, rapamycin-induced TORC1 inactivation, nuclear vacuolar junction (NVJ) expansion, and nuclear fibrillary lamina defects (Bo Otto and Thumm, 2020). In 2009, it was first reported that LMNA/C is involved in the development of mammalian nuclear autophagy.…”