Hereditary spastic paraplegia: mitochondrial metalloproteases of yeast

Hereditary spastic paraplegia (HSP) is a genetically heterogenous group of inherited neurodegenerative disorders. Recently, an autosomal recessive for m of HSP was mapped to 16q24.3, and subsequently the defective gene associa ted to HSP was identified and designated SPG7. The SPG7 gene product was pr edicted to encode a protein of 795 amino acids, and is called paraplegin. P araplegin is highly homologous to a class of well studied yeast ATP-depende nt zinc metalloproteases, which show 55%, 55% and 52% identity, respectivel y, to Afg3p, Rca1p and Yme1p. Mutation of either Afg3p, Rca1p or Yme1p in y east results in pleiotropic effects with regard to growth, respiration and, particularly, in the assembly and/or degradation of more than one mitochon drial protein complex. Taking into account the homology of paraplegin to th ese yeast ATP-dependent zinc metalloproteases and what is known about their function, allows us to speculate as to what function paraplegin plays in n ormal individuals.