Abstract

Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typically excluded during conventional macronucleophagy and micronucleophagy, indicating that degradation of nuclear cargo is tightly regulated. In mammals, similarly to other autophagy subtypes, nucleophagy is crucial for cellular differentiation and development, in addition to enabling cells to respond to various nuclear insults and cell cycle perturbations. A common denominator of all nucleophagic processes characterized in diverse organisms is the dependence on the core autophagic machinery. Here, we survey recent studies investigating the autophagic processing of nuclear components. We discuss nucleophagic events in the context of pathology, such as neurodegeneration, cancer, DNA damage, and ageing.

Highlights

  • Autophagy is an evolutionarily conserved catabolic process enabling cells to maintain homeostasis as well as respond to stress conditions

  • Either autophagy inhibition or LC3-lamin B1 interaction inhibition impair lamin B1 degradation and interestingly, attenuate oncogene-induced senescence in human cells (Dou et al, 2015). These findings suggest that autophagic degradation of a nuclear lamina component could protect cells from tumorigenesis

  • Similar to endoplasmic reticulum (ER)-phagy, macronucleophagy involves bulging of the nuclear envelope and budding of the micronucleus

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Summary

Introduction

Autophagy is an evolutionarily conserved catabolic process enabling cells to maintain homeostasis as well as respond to stress conditions. Nucleophagy is the degradation of nuclear material including nuclear membrane, nuclear lamina, nucleoplasm, nucleolus and DNA by the autophagic machinery. During macronucleophagy the nuclear cargo receptor, autophagy related protein (Atg) 39, Nucleophagy which localizes to both inner and outer nuclear membrane (INM and ONM, respectively), the perinuclear endoplasmic reticulum (ER), and decorates macronucleophagy cargo, interacts with Atg8, a well-established marker of the autophagic membrane.

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