Why just eat in, when you can also eat out?

Abstract

The current working definition of autophagy is the following: all processes in which intracellular material is degraded within the lysosome/vacuole and where the macromolecular constituents are recycled. There are several ways to classify the different types of autophagy. For example, we can separate autophagy into two primary types, based on the initial site of cargo sequestration. In particular, during microautophagy and chaperone-mediated autophagy, uptake occurs directly at the limiting membrane of the lysosome or vacuole. In contrast, macroautophagy—whether selective or nonselective—and endosomal microautophagy involve sequestration within an autophagosome or an omegasome, or late endosomes/multivesicular bodies, respectively; the key point being that in these types of autophagy the initial sequestration event does not occur at the limiting membrane of the degradative organelle. In any case, the cargo is ultimately delivered into the lysosome or vacuole lumen for subsequent degradation. Thus, I think most autophagy researchers view the degradative organelle as the ultimate destination of the pathway. Indeed, this fits with the general concept that organelles allow reactions to be compartmentalized. With regard to the lysosome or vacuole, this also confers a level of safety by keeping the lytic contents away from the remainder of the cell. If we are willing to slightly modify our definition of autophagy, with a focus on “degradation of a cell’s own components through the lysosomal/vacuolar machinery,” we can include a newly documented process, programmed nuclear destruction (PND).

Keywords: :

• autophagy
• lysosome
• meiosis
• spore
• stress
• vacuole

PND involves the degradation of intracellular material in a vacuolar hydrolase-dependent manner, followed by recycling of the breakdown products.¹ The only catch with regard to the definition of autophagy is that the breakdown does not occur within the vacuole. Instead, the vacuole is ruptured or permeabilized, allowing the release of the lytic contents into the cytosol in a process referred to as “mega-autophagy.”²

During sporulation in Saccharomyces cerevisiae the cell undergoes dramatic remodeling in an autophagy-dependent process (many of the initial ATG genes were cloned based on this phenotype, relying on complementation of the sporulation defect of the respective loss-of-function mutations). Following meiosis, the four haploid products are packaged into a four-spore tetrad. However, it turns out that the generation of tetrads occurs primarily under optimized laboratory conditions; under more nutrient-limiting conditions, yeast typically produce two-spore dyads. So what happens to the remaining two products of meiosis? As highlighted in a punctum in this issue of the journal, the nuclei that are not used to form spores are degraded following permeabilization of the vacuole; the breakdown products can then be used to provide nutrients for the spores upon germination, or for neighboring cells to fuel more productive meiosis. Some aspects of PND, such as the generation of nucleosomal ladders, resemble apoptosis, suggesting that this may represent a more general type of developmental process that could benefit the surrounding cells in a colony. This is perhaps also the reason that the process underlying PND has also been termed “sporoptosis,” reminiscent of programmed cell death (PCD), rather than “sporophagy,” since it may represent an intermediate pathway that includes aspects of both PCD and autophagy.

Thus, if we include PND as a type of autophagy—certainly a noncanonical one—we expand the range of processes in which autophagic (self-eating) degradation plays a role.³ In that case, we no longer have to limit our view of autophagy as being confined to eating within the lysosome or vacuole; sometimes cells, like us, prefer to eat out.