The intricacy of nuclear membrane dynamics during nucleophagy

Abstract

The nucleus is a site of a number of essential metabolic activities relating to maintenance and expression of the genome. Such activities include: DNA replication, recombination and repair, gene transcription, RNA processing and ribosome subunit maturation and assembly. 1,2 In order for these essential activities to be carried out in a correct and efficient manner the corresponding machinery must be maintained. Consequently, it is to be expected there are processes within cells which act to 'repair' nuclear damage through the coordinated removal of damaged non-functional components, or those surplus to requirement. A growing body of evidence indicates that parts of the nucleus can be specifically degraded by nucleophagy (micronucleophagy), an autophagic process involving localized changes in membrane organization and dynamics. Here, we discuss nucleophagy in this context as well as its role in 'housecleaning' during nutrient Nuclear Structure, Function and CompartmentalizationThe nucleus is not only the largest membrane-enclosed organelle in eukaryotic cells, but arguably the most elaborate. Two main structures make up the metazoan (including mammalian) nucleus. The first of these is the nuclear envelope (NE) that acts as the interface between the nucleus and the rest of the cell enclosing the contents of the nucleus. 3,4 The second is the nuclear lamina, a dense but fenestrated network composed of intermediate filaments made of lamins and lamin-associated (e.g., emerin) proteins underlying the inner surface of the NE. The NE is required for maintenance of nuclear shape, spacing of nuclear pore complexes (NPCs), organization of heterochromatin, DNA replication and regulation of transcription factors (Fig. 1). [5][6][7][8][9][10][11] Certain organisms, such as fungi or plants lack lamins 12 and consequently lack a nuclear lamina. 13 Plants contain coiled-coil proteins, apparently unrelated to lamins, which serve as nucleoskeleton components.12,14,15 Coiled-coil proteins have been implicated also as nucleoskeleton components in non-metazoans, notably yeast and Trypanosoma brucei. 12,16,17 The NE is comprised of two concentric, closely opposed lipid bilayers, the outer and inner nuclear membranes (ONM and INM, respectively). 4,18 The ONM is continuous with the rough endoplasmic reticulum (rER), studded with ribosomes and functions in secretion and lipid biosynthesis. The ribosome-free INM faces the viscous nucleoplasm, and contains a unique spectrum of integral and membrane-associated proteins that provide binding sites for the nuclear lamina and chromatin. The ONM and INM are separated by a luminal space but become contiguous at sites of high membrane curvature occupied by the NPCs (Fig. 1). NPCs exclusively mediate and regulate nucleocytoplasmic trafficking, the signal-dependent, bidirectional trafficking of macromolecules between the nucleus and cytoplasm which is crucial for both gene expression and chromosomal maintenance. 7,[18][19][20] The interior of the nucleus lacks membrane-bound subcompartments, but is...

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