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About the Cover

Cover Figure


Cover  The selective and nonselective (bulk) degradation of cytosol and organelles in animal lysosomes and yeast vacuoles is called autophagy (self-eating). In the last decade, the study of autophagy has seen a renaissance with the discovery and analysis of yeast autophagy genes, many of which are conserved (Reggiori and Klionsky. [2002]. Euk. Cell 1, 11-21). A number of autophagy genes are required for macroautophagy and, in yeast, the related Cvt pathway, both of which involve the formation of double membrane vesicles that deliver their cargo by fusing with the vacuole membrane. Less is known about the molecular genetics of microautophagy. Microautophagy does not involve any vesicular intermediates; instead, cargo is engulfed directly into invaginations of the vacuole membrane. Autophagy is best known as a starvation response but is also employed for other purposes. For example, peroxisomes that accumulate when yeast are fed fatty acids are selectively degraded by autophagy when glucose becomes available. Autophagy also plays a prominent role in the programmed cell deaths of neurons and during metamorphosis in insects (Lockshin and Zakeri. [2002]. Curr. Opin. Cell Biol. 14, 727-733). Because the nucleus is an essential organelle, it had not been considered a substrate for autophagy until the discovery, in Saccharomyces cerevisiae, of piecemeal microautophagy of the nucleus (PMN) (Roberts et al., [2003]. Mol. Biol. Cell 14, 129-141). During PMN, teardrop-like portions of the nucleus called blebs are pinched off by the vacuole membrane and released into the lumen as PMN vesicles. Consistent with PMN not being a lethal event, chromosomal DNA is excluded from the blebs and vesicles of both rapidly growing and starving cells. PMN occurs in the context of nucleus-vacuole (NV) junctions, which are Velcro-like patches formed between Vac8p in the vacuole membrane and Nvj1p in the nuclear membrane (Pan et al., [2002]. Mol. Biol. Cell 11, 2445-2457). It is not known if PMN-like processes occur in higher cells. This month's cover shows a time course involving nine images, taken at 90-sec intervals, of a mitotic cell undergoing active PMN. In this cell Nvj1p is tagged with green fluorescent protein (GFP), and the vacuole membrane is stained red with FM4-64. The entire nuclear envelope is stained green because Nvj1p-GFP is overexpressed and leaked outside the boundary of the NV junction, PMN blebs, and vesicles appear yellow. Note the mobility of PMN vesicles as they move in and out of the focal plane in the vacuole lumen.---David Goldfarb


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