Import of small Tim proteins into the mitochondrial intermembrane space

AUTOR(ES)

Lutz, Thomas

FONTE

Oxford University Press

RESUMO

Proteins of the intermembrane space (IMS) of mitochondria are typically synthesized without presequences. Little is known about their topogenesis. We used Tim13, a member of the ‘small Tim protein’ family, as model protein to investigate the mechanism of translocation into the IMS. Tim13 contains four conserved cysteine residues that bind a zinc ion as cofactor. Import of Tim13 did not depend on the membrane potential or ATP hydrolysis. Upon import into mitochondria Tim13 adopted a stably folded conformation in the IMS. Mutagenesis of the cysteine residues or pretreatment with metal chelators interfered with folding of Tim13 in vitro and impaired its import into mitochondria. Upon depletion of metal ions or modification of cysteine residues, imported Tim13 diffused back out of the IMS. We propose an import pathway in which (1) Tim13 can pass through the TOM complex into and out of the IMS in an unfolded conformation, and (2) cofactor acquisition stabilizes folding on the trans side of the outer membrane and traps Tim13 in the IMS, and drives unidirectional movement of the protein across the outer membrane of mitochondria.

Documentos Relacionados

• An internal targeting signal directing proteins into the mitochondrial intermembrane space
• Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins
• Mitochondrial Import of the ADP/ATP Carrier: the Essential TIM Complex of the Intermembrane Space Is Required for Precursor Release from the TOM Complex
• Import of cytochrome c heme lyase into mitochondria: a novel pathway into the intermembrane space.
• Role of the intermembrane-space domain of the preprotein receptor Tom22 in protein import into mitochondria.