How Autophagy Feeds Cancer’s Need for Metabolites

Illustration of energy metablism in cell.Metabolism underpins numerous cellular processes. Without it, cells would not grow, divide, synthesize or secrete. Another pathway, autophagy, degrades unwanted cellular materials, helping to maintain cell health. With these opposing roles, is there a connection between autophagy and metabolism? As it turns out, the answer is yes. Because molecules degraded by autophagy are recycled and fed into metabolism pathways as precursor compounds. There are interesting implications as a result of this connection, ones that affect cancer cells as described in a recent Cell Metabolism review article.

Autophagic flux, the process by which molecules and organelles are directed to the autophagosome, fuse with the lysosome and are degraded, involves a selective process that determines the cargo carried within the autophagosome. Autophagy-related genes (ATGs) direct the process and particular receptor proteins bind the cargo. What is interesting about the connection among cancer, autophagy and metabolism is the complexity of the role that autophagy plays in cancer. While autophagy was thought to act in a more tumor suppressive manner as shown when one copy of an ATG6 analogous gene in mice was deleted and the other left unaltered, and malignant tumors developed, but in mice mosaic for ATG5 deletions, the inhibition of autophagy resulted in benign tumors in the liver. This latter experiment suggested autophagy was needed for cancer progression, a hypothesis reinforced by the lack of ATG mutations in human cancers. Continue reading

Autophagy: The Intersection of Vitamin D, HIV and Tuberculosis

HIV-1 particles assembling at the surface of an infected macrophage. By see Source [CC-BY-2.5 (http://creativecommons.org/licenses/by/2.5)], via Wikimedia Commons

With the warmer season in full swing in Wisconsin, the grass needs mowing and the weeds need pulling. As a consequence, I am outside in the sun, synthesizing Vitamin D (and watching my freckles multiply). The benefits of this vitamin have been discussed in the news (e.g., may help prevent cancer, maintains a healthy working brain) while informing us most people lack adequate levels. A recent PLoS Pathogens article intrigued me because the researchers examined the role Vitamin D played in mitigating human immunodeficiency virus type-1 (HIV) and Mycobacterium tuberculosis coinfection in macrophages.

Why were Campbell and Spector interested in Vitamin D’s effect on HIV-1 and M. tuberculosis? Continue reading