Translating m-AAA protease function in mitochondria to hereditary spastic paraplegia

Trends Mol Med. 2006 Jun;12(6):262-9. doi: 10.1016/j.molmed.2006.04.002. Epub 2006 May 2.


Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurodegenerative disorder that is characterized by progressive and cell-specific axonal degeneration. An autosomal recessive form of the disease is caused by mutations in paraplegin, which is a conserved subunit of the ubiquitous and ATP-dependent m-AAA protease in mitochondria. The m-AAA protease carries out protein quality control in the inner membrane of the mitochondria, suggesting a pathogenic role of misfolded proteins in HSP. A recent study demonstrates that the m-AAA protease regulates ribosome assembly and translation within mitochondria by controlling proteolytic maturation of a ribosomal subunit. Here, we will discuss implications of the dual role of the m-AAA protease in protein activation and degradation for mitochondrial dysfunction and axonal degeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Animals
  • Axons / enzymology*
  • Axons / pathology
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mice
  • Mice, Knockout
  • Mitochondria / enzymology*
  • Mitochondria / pathology
  • Mitochondrial Membranes / enzymology
  • Models, Animal
  • Mutation
  • Phenotype
  • Protein Folding
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spastic Paraplegia, Hereditary / enzymology*
  • Spastic Paraplegia, Hereditary / genetics
  • Spastic Paraplegia, Hereditary / pathology


  • MrpL32 protein, S cerevisiae
  • Ribosomal Proteins
  • Saccharomyces cerevisiae Proteins
  • Metalloendopeptidases
  • SPG7 protein, human
  • m-AAA proteases
  • ATPases Associated with Diverse Cellular Activities