Hereditary spastic paraplegia: respiratory choke or unactivated substrate?

Defects in the mitochondrial AAA protease family member, paraplegin, result in an autosomal recessive form of hereditary spastic paraplegia (HSP). In this issue of Cell, Nolden et al. (2005) report a new molecular mechanism for HSP based on the requirement of paraplegin for the proteolysis of a specific mitochondrial ribosomal protein. The processing of this substrate is required for robust translation in mitochondria.