Macroautophagy (hereafter autophagy) is a conserved membrane trafficking pathway responsible for the turnover of cytosolic protein and organelles during periods of nutrient deprivation. This pathway is also linked to a number of processes important for human health, including tumor suppression, innate immunity and the clearance of protein aggregates. As a result, there is tremendous interest in autophagy as a potential point of therapeutic intervention in a variety of pathological states. To achieve this goal, it is imperative that we develop a thorough understanding of the normal regulation of this process in eukaryotic cells. The Tor protein kinases clearly constitute a key element of this control as Tor activity inhibits this degradative process in all organisms examined, from yeast to man. Here, we discuss recent work indicating that the cAMP-dependent protein kinase (PKA) also plays a critical role in controlling autophagy in the budding yeast, Saccharomyces cerevisiae. A model describing how PKA activity might influence this degradative process, and how this control might be integrated with that of the Tor pathway, is presented.
JS Stephan, YY Yeh, V Ramachandran, SJ Deminoff, PK Herman. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proc Natl Acad Sci U S A 2009; 106: 17049- 54.
PMID: 19805182 DOI: 10.1073/pnas.0903316