Abstract
Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded. This process has become a major focus of biological and biomedical research with thousands of papers published each year and rapidly growing appreciation that autophagy affects many normal and pathological processes. However, as we learn more about this evolutionarily ancient process, we are discovering that autophagy's effects may work for both the good and the bad of an organism. Here, I discuss some of these context-dependent findings and how, as we make sense of them, we can try to apply our knowledge for practical purposes.
Highlights
Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded
As I started on this essay, I googled ‘‘double-edged sword autophagy’’ and got pages of references to articles and books making the point that sometimes autophagy is good and sometimes it’s bad
Knockout or knockdown of autophagyrelated proteins (ATGs) can be a highly effective way to inhibit autophagy, many, perhaps all, ATGs have other functions as well [11]. This means that if your ATG knockout had a phenotype, it could be due to other functions of that protein rather than blocking autophagy
Summary
Autophagy is the mechanism by which cellular material is delivered to lysosomes and degraded. Most of the articles were linking the doubleedged sword metaphor to diseases such as cancer, diabetes, infection, neurological disease, ischemic injury, etc This implies that if we understand when autophagy is a good thing and when it’s a bad thing, it will be feasible to improve treatment or prevention of these diseases by manipulating autophagy up or down. Attempts to do this in people are already underway. Knockout or knockdown of ATGs can be a highly effective way to inhibit autophagy, many, perhaps all, ATGs have other functions as well [11] This means that if your ATG knockout had a phenotype, it could be due to other functions of that protein rather than blocking autophagy. With these definitions and caveats noted, I will try to make two points. (1) Autophagy is both good and bad in different circumstances. (2) By understanding the mechanisms that underlie these divergent effects, we can start to see how we can apply this knowledge in a rational way to get outcomes that we want, such as effective treatments for the diseases where autophagy plays a role
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