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Mitochondria regulate autophagy by conserved signalling pathways
Author(s) -
Graef Martin,
Nunnari Jodi
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.104
Subject(s) - autophagy , biology , autophagy related protein 13 , microbiology and biotechnology , mitochondrion , bag3 , flux (metallurgy) , protein kinase a , neurodegeneration , kinase , biochemistry , mitogen activated protein kinase kinase , chemistry , apoptosis , medicine , disease , organic chemistry , pathology
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.