The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria

Cell. 2005 Oct 21;123(2):277-89. doi: 10.1016/j.cell.2005.08.003.


AAA proteases comprise a conserved family of membrane bound ATP-dependent proteases that ensures the quality control of mitochondrial inner-membrane proteins. Inactivation of AAA proteases causes pleiotropic phenotypes in various organisms, including respiratory deficiencies, mitochondrial morphology defects, and axonal degeneration in hereditary spastic paraplegia (HSP). The molecular basis of these defects, however, remained unclear. Here, we describe a regulatory role of an AAA protease for mitochondrial protein synthesis in yeast. The mitochondrial ribosomal protein MrpL32 is processed by the m-AAA protease, allowing its association with preassembled ribosomal particles and completion of ribosome assembly in close proximity to the inner membrane. Maturation of MrpL32 and mitochondrial protein synthesis are also impaired in a HSP mouse model lacking the m-AAA protease subunit paraplegin, demonstrating functional conservation. Our findings therefore rationalize mitochondrial defects associated with m-AAA protease mutants in yeast and shed new light on the mechanism of axonal degeneration in HSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / deficiency
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mitochondria / enzymology*
  • Mitochondrial Membranes / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Mutation
  • Protein Biosynthesis
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Spastic Paraplegia, Hereditary / enzymology*
  • Spastic Paraplegia, Hereditary / genetics
  • Substrate Specificity


  • MrpL32 protein, S cerevisiae
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Metalloendopeptidases
  • Spg7 protein, mouse
  • m-AAA proteases
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities