Autophagy 101

By Bruce Lieberman
September 5, 2011
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Every well-run house needs someone to clean up the clutter, prune the hedges, and rake up the leaves, even whip up something to eat when the refrigerator is empty. In the life of a cell, those kinds of jobs are handled by an incredible process called autophagy.

Biologists first observed autophagy in the early 1960s as a mechanism by which cells break down their own components and recycle the parts. Autophagy, which literally means “to eat oneself,” is essential to cell survival, particularly when food is scarce.

But there’s a much larger role for autophagy than just helping a cell survive starvation. The process helps cells dispose of malfunctioning parts, clean up clutter, and defend against invading pathogens.

Autophagy is always at work in a cell, but the process ramps up during times of stress. However, too much or too little of the process has been connected to disease. For example, when autophagy falls short, cancer can develop. In fact, some cancer cells also hijack autophagy to survive in a dormant state—only to begin growing again when nutrients become available. In Parkinson’s disease, the build-up of toxic proteins can overwhelm the ability of the cell’s autophagy machinery to digest them. Alzheimer’s disease, researchers have found, can also sabotage the process.

Autophagy begins inside cells with the formation of a vesicle called an autophagosome, which gobbles up the part of the cell targeted for digestion—somewhat like a Pac-Man. The autophagosome then fuses with another structure in the cell called a lysosome, basically a bag of enzymes that helps the autophagosome break down proteins and other molecules that can then be recycled (see cartoon at below).

Autophagy cartoon adapted from: Meléndez, A. and Levine, B. Autophagy in C. elegans (August 24, 2009), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.147.1, http://www.wormbook.org.

Scientists first identified some of the genes that control autophagy in the 1990s, but the picture is becoming increasingly complex. A 2010 study published in Nature found that autophagy in human cells engages 409 different proteins interacting in 751 ways—and scientists are just beginning to scratch the surface in understanding the role each plays in human health and disease.

For more information, read Focusing on Autophagy, a review article that appeared in the September 2010 issue of Nature Cell Biology.

To read more about autophagy research at Sanford-Burnham, check out these blog posts:
Cellular Feast or Famine
The Truth About AMPK

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