Mitochondria regulate autophagy by conserved signalling pathways

Martin Graef, Jodi Nunnari

Research output: Contribution to journalArticle

112 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2101-2114
Number of pages14
JournalEMBO Journal
Volume30
Issue number11
DOIs
StatePublished - Jun 1 2011

Fingerprint

Mitochondria
Autophagy
Cyclic AMP-Dependent Protein Kinases
Genes
Fluxes
Phosphotransferases
Sirolimus
Yeast
Protein Kinases
Quality control
Aging of materials
Amino Acids
Starvation
Quality Control
Saccharomyces cerevisiae
Homeostasis

Keywords

  • autophagy regulation
  • mitochondria
  • protein kinase A
  • TOR

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Mitochondria regulate autophagy by conserved signalling pathways. / Graef, Martin; Nunnari, Jodi.

In: EMBO Journal, Vol. 30, No. 11, 01.06.2011, p. 2101-2114.

Research output: Contribution to journalArticle

Graef, Martin ; Nunnari, Jodi. / Mitochondria regulate autophagy by conserved signalling pathways. In: EMBO Journal. 2011 ; Vol. 30, No. 11. pp. 2101-2114.
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