Starvation-induced Autophagy Discovered to Be Selective

New research from scientists at Harvard Medical School surveyed the protein landscape of cells in an attempt to understand the underlying mechanisms of starvation-induced autophagy. The results were published in Nature. 

The team used quantitative global translatome, degradome proteomics and Ribo-Halo to examine cells in conditions of acute nutrient stress. Through their analyses—where they examined the degradation of more than 8,300 proteins—they built a quantitative framework that describes degradative mechanisms and proteome remodelling in conditions of nutrient deficiency. 

They discovered that autophagy is a selective degradation process. “When cells are starving, they don't haphazardly degrade ribosomes en masse through autophagy. Instead, they appear to have mechanisms to control what they recycle," adds senior study author Wade Harper. They also identified that the primary factor that led to lower ribosome levels was a reduction in new ribosome synthesis and turnover through non-autophagy dependent pathways. 

The data gathered concluded that the pattern of ribosome turnover seemed to be independent of autophagy and matched proteins that are known to be degraded via the ubiquitin-proteasome system instead. "Our understanding of autophagy is incomplete, and many aspects are still unclear," co-first author Heeseon An adds. "Controlling autophagy is being explored in a wide range of contexts such as killing tumor cells by starving them of key nutrients or allowing neurons to remove harmful protein aggregates."