- Proteins and Peptides
- Lysates and Cell Lines
By Christina Towers, PhD
Autophagy is the catabolic process that degrades cytoplasmic material via the lysosome. In the beginning... the process of macroautophagy was originally characterized in yeast where the core autophagy proteins or Apgs were identified. In this first system, the multistep process of phagophore initiation and elongation as well as the conjugation machinery that mediate efficient autophagosome completion were determined and cloned to assess function. The mechanisms of starvation induced autophagy as well as many of the selective autophagy processes were also hashed out in yeast. Homologues to all of these core autophagy proteins have now been identified in other model organisms as well as higher eukaryotes including Drosophila melanogaster, Caenorhabditis elegans, Zebra fish, mice, and humans1,2.
|Induction||Nucleation, Phagophore Formation||Elongation, Autophagosome Formation|
Throughout biology, model organisms have played an instrumental role in defining key molecular mechanisms that eventually lead to pathological relevance, and autophagy is no different. For example, it was shown in C. elegans that paternal mitochondria are degraded by autophagy in developing embryos3,4 – a finding that answered the age-old question of why only maternal mitochondria are inherited in eukaryotes. Autophagy was also first associated with longevity and increased life span in C. elegans, where genetic inhibition of many core autophagy proteins could suppress the extended life phenotype induced by dietary restriction5,6.
High impact findings have also been noted in Drosophila models where autophagy in the tumor microenvironment was shown to be sufficient to initiate dormant tumor growth7. These findings and many others have set the ground work for more physiologically relevant studies in zebra fish, mouse models, and human cell lines.
Despite the multitude of caveats associated with mouse models including long gestation periods, small cohorts size, restricted embryo accessibility, as well as overall cost, they are still the dominant model organism used to study autophagy particularly in the context of cancer and neurodegenerative diseases. However, alternative models provide an increasing number of advantages, particularly for studying basic cell biology processes like autophagy.
Christina Towers, PhD
University of Colorado (AMC)
Dr. Towers studies the roles of autophagy, apoptosis and cell death in cancer.