Figure 7.

A stop-transfer pathway for the import and activation of DIABLO by mitochondria. (A) The precursor form of DIABLO (black) is synthesized in the cytosol and the N-terminal presequence recognized by the TOM complex and thereby transferred across the outer membrane. Engaged in the TIM23 complex, DIABLO might be processed by the matrix-located peptidase, such as mitochondrial processing peptidase, and is processed by the IMP complex composed of Imp1, Imp2, and Som1. Release of processed DIABLO into the intermembrane space allows for its assembly into a dimer and its availability for release into the cytosol only if the outer membrane is ruptured. (B) The presequences of DIABLO (top schematic) and Cytb₂ (bottom schematic) show similar regions corresponding to a basic amphipathic helix with the matrix targeting information (gray) and the intermembrane sorting sequence, containing a core of hydrophobic residues (dark gray) preceded by a cluster of three positively charged residues (black) important for recognition of the sorting sequence. For DIABLO the IMP1 processing site is designated between C⁵³ and A⁵⁴ and for Cytb between N⁸⁰ and E⁸¹.