title: Mitochondria regulate autophagy by conserved signalling pathways.
abstract: Autophagy is a conserved degradative process that is crucial for cellular homeostasis and cellular quality control via the selective removal of subcellular structures such as mitochondria. We demonstrate that a regulatory link exists between mitochondrial function and autophagy in Saccharomyces cerevisiae. During amino-acid starvation, the autophagic response consists of two independent regulatory arms-autophagy gene induction and autophagic flux-and our analysis indicates that mitochondrial respiratory deficiency severely compromises both. We show that the evolutionarily conserved protein kinases Atg1, target of rapamycin kinase complex I, and protein kinase A (PKA) regulate autophagic flux, whereas autophagy gene induction depends solely on PKA. Within this regulatory network, mitochondrial respiratory deficiency suppresses autophagic flux, autophagy gene induction, and recruitment of the Atg1-Atg13 kinase complex to the pre-autophagosomal structure by stimulating PKA activity. Our findings indicate an interrelation of two common risk factors-mitochondrial dysfunction and autophagy inhibition-for ageing, cancerogenesis, and neurodegeneration.
authors.affiliation: Department of Molecular and Cellular Biology, Davis University of California, Davis, CA, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Graef
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D019069:Cell Respiration; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000596:Amino Acids; D000071183:Autophagy-Related Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C500749:target of rapamycin protein, S cerevisiae; D017868:Cyclic AMP-Dependent Protein Kinases