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An intersubunit signaling network coordinates ATP hydrolysis by m-AAA proteases.

Ring-shaped AAA+ ATPases control a variety of cellular processes by substrate unfolding and remodeling of macromolecular structures. However, how ATP hydrolysis within AAA+ rings is regulated and coupled to mechanical work is poorly understood. Here we demonstrate coordinated ATP hydrolysis within m-AAA protease ring complexes, conserved AAA+ machines in the inner membrane of mitochondria. ATP binding to one AAA subunit inhibits ATP hydrolysis by the neighboring subunit, leading to coordinated rather than stochastic ATP hydrolysis within the AAA ring. Unbiased genetic screens define an intersubunit signaling pathway involving conserved AAA motifs and reveal an intimate coupling of ATPase activities to central AAA pore loops. Coordinated ATP hydrolysis between adjacent subunits is required for membrane dislocation of substrates, but not for substrate processing. These findings provide insight into how AAA+ proteins convert energy derived from ATP hydrolysis into mechanical work.

Pubmed ID: 19748354


  • Augustin S
  • Gerdes F
  • Lee S
  • Tsai FT
  • Langer T
  • Tatsuta T


Molecular cell

Publication Data

September 11, 2009

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI076239
  • Agency: NIAID NIH HHS, Id: R01 AI076239-02
  • Agency: NIGMS NIH HHS, Id: R01 GM067672
  • Agency: NIGMS NIH HHS, Id: R01 GM067672-05

Mesh Terms

  • ATP-Dependent Proteases
  • Adenosine Triphosphatases
  • Adenosine Triphosphate
  • Allosteric Regulation
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Conserved Sequence
  • Energy Metabolism
  • Fungal Proteins
  • Humans
  • Hydrolysis
  • Kinetics
  • Metalloendopeptidases
  • Mitochondrial Membranes
  • Models, Molecular
  • Molecular Sequence Data
  • Point Mutation
  • Protein Subunits
  • Signal Transduction
  • Structure-Activity Relationship
  • Substrate Specificity
  • Yeasts