Abstract
Mitochondrial preproteins synthesized in the cytosol are imported through the mitochondrial outer membrane by the translocase of the outer mitochondrial membrane (TOM) complex. Tom40 is the major component of the complex and is essential for cell viability. We generated 21 different mutations in conserved regions of the Neurospora crassa Tom40 protein. The mutant genes were transformed into a tom40 null nucleus maintained in a sheltered heterokaryon, and 17 of the mutant genes gave rise to viable strains. All mutations reduced the efficiency of the altered Tom40 molecules to assemble into the TOM complex. Mitochondria isolated from seven of the mutant strains had defects for importing mitochondrial preproteins. Only one strain had a general import defect for all preproteins examined. Another mutation resulted in defects in the import of a matrix-destined preprotein and an outer membrane beta-barrel protein, but import of the ADP/ATP carrier to the inner membrane was unaffected. Five strains showed deficiencies in the import of beta-barrel proteins. The latter results suggest that the TOM complex distinguishes beta-barrel proteins from other classes of preprotein during import. This supports the idea that the TOM complex plays an active role in the transfer of preproteins to subsequent translocases for insertion into the correct mitochondrial subcompartment.
Highlights
Following the initial recognition and translocation of mitochondrial preproteins through the outer membrane, most preproteins interact with one of three sorting translocase complexes for targeting and assembly to the correct mitochondrial subcompartment
Proteins destined for the mitochondrial matrix interact with the TIM23 complex (Translocase of the Inner mitochondrial Membrane), carrier proteins of the inner membrane interact with the TIM22 complex [3, 5, 13,14,15,16]. -Barrel preproteins of the outer membrane are inserted into the membrane via the TOB/SAM (Topogenesis of mitochondrial Outer membrane -barrel proteins or Sorting and Assembly Machinery) complex [17,18,19]
Tom40 is the major component of the the outer mitochondrial membrane (TOM) complex and forms the pore through which preproteins traverse the outer membrane (9, 26 –28)
Summary
Fungal Genetics Stock Center no. 2489 (74-OR23-1VA) Fungal Genetics Stock Center no. 7255 Fungal Genetics Stock Center no. 7265 Transformation of the host V strain In addition to its structural role as the pore-forming component of the TOM complex, Tom has been shown to have several other functions that are important for the process of importing mitochondrial preproteins. The TOB/SAM complex inserts Tom into the outer membrane where it associates with another molecule of Tom and Tom to form a 100-kDa assembly intermediate. Further association with Tom, Tom, Tom, and additional molecules of Tom give rise to the fully assembled 400-kDa TOM core complex This pathway of assembly first described in fungal systems seems to be generally conserved in human mitochondria [33]. Mim1/Tom13 [44, 45] and Mdm10 [46], play a role in assembly of Tom following interaction with the TOB/SAM complex. In this study we describe the effects of changing several regions containing conserved residues of Tom on the assembly, stability, and function of the TOM complex
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