Señalización por nutrientes y autofagia en "Schizosaccharomyces pombe"

Abstract

Molecular mechanisms that induce autophagy during glucose starvation have been extensively explored in the budding yeast Saccharomyces cerevisiae, nonetheless little is known about how this process is regulated in the evolutionary distant fission yeast Schizosaccharomyces pombe. Here, we show that S. pombe autophagy in response to glucose limitation relies on an entirely functional mitochondrial Electron Transport Chain (ETC). We also found that the cAMP-PKA signaling pathway acts as a repressor of autophagy in the presence of glucose, and this regulatory mechanism is likely exerted both at transcriptional (downregulating the transcription factor Rst2 (Carbon Catabolite Repression (CCR)) and post-transcriptional levels. On the other hand, the stress-activated protein kinase (SAPK) signaling pathway modulates positively autophagy upon glucose limitation at the transcriptional level through its downstream effector Atf1 and by direct in vivo phosphorylation of Rst2. Contrary to S. cerevisiae, the AMP-activated protein kinase (AMPK) and DNA damage response pathway components do not modulate fission yeast autophagic flux under these conditions. Thus, our data indicate that the signaling pathways that govern autophagy during glucose starvation have evolved differently in S. pombe and uncover the existence of sophisticated and multifaceted mechanisms that control this self-preservation and survival response.