Johannes M Herrmann

..We conclude that Mba1 is part of the mitochondrial protein export machinery and represents the first component of a novel Oxa1-independent insertion pathway into the mitochondrial inner membrane...

..We propose that these chaperones, Mss51 for subunit 1 and Cox20 for subunit 2, control the coordinate assembly process to prevent potentially harmful redox reactions of unassembled or misassembled subunits...

..The second class depends on the energy gain of protein folding, and the third on the association of the proteins to high-affinity binding sites in the IMS...

..Our observations rather suggest that the dependence on Oxa1 correlates with the net charge of the domain that has to be translocated across the lipid bilayer...

..We suggest that this process reflects the evolutionary origin of the IMS from the periplasmic space of the prokaryotic ancestors of mitochondria...

..Our results are consistent with a gene-duplication event in gram-positive bacteria that enabled the specialization of a YidC isoform that mediates cotranslational activity independent of an SRP pathway...

..We propose that Mba1 functions as a ribosome receptor that cooperates with Oxa1 in the positioning of the ribosome exit site to the insertion machinery of the inner membrane...

..Our observations suggest that during evolution of mitochondria from their bacterial ancestors the two descendents of YidC functionally segregated to perform two distinct activities, one co-translational and one post-translational...

..On the basis of these observations we propose that charged residues in Tim17 are critical for the preprotein-induced gating of the TIM23 translocase...

..We propose that proline residues, together with the hydrophobicity of the TMD and the presence of charged residues COOH-terminally flanking the TMD, are determinants of the intramitochondrial sorting of inner membrane proteins...

..In mitochondria as well as in vitro, Hot13 can be functionally replaced by zinc-binding chelators. We propose that Hot13 maintains Mia40 in a zinc-free state, thereby facilitating its efficient oxidation by Erv1...

..The methods described here can be applied also to the study of other aspects of organelle biogenesis such as folding, assembly, and degradation of proteins...

..Furthermore, Mia40 directly interacts with newly imported Tim13 protein. We conclude that Mia40 is the first essential component of a specific translocation pathway of metal-binding IMS proteins...

..These observations show a critical role for Guf1 in vivo. The observed defects in Guf1-deficient mitochondria are consistent with a function of Guf1 as a fidelity factor of mitochondrial protein synthesis...

..This review summarizes the present knowledge on the import and sorting of mitochondrial precursor proteins, with a special emphasis on unresolved questions and topics of current research...

..This suggests that co-translational membrane insertion of mitochondrial translation products is facilitated by a physical interaction of translation complexes with the membrane-bound translocase...

..Our observations suggest that Grx6 and Grx7 do not play a general role in the oxidative folding of proteins in the early secretory pathway but rather counteract the oxidation of specific thiol groups in substrate proteins...

..Thus, Erv1 represents an unusual type of substrate of the Mia40-dependent import pathway...

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..The requirement for post-translational transport to their final destination has placed considerable constraints on the evolution of mitochondrial protein sequences...

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..coli, we show here that Cox18 is able to complement the essential Sec-independent function of YidC. This identifies Cox18 as a bona fide member of the YidC/Oxa1/Alb3 family...

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..Thus, analogous to the system in the bacterial periplasm, the disulfide relay in the intermembrane space is connected to the electron transport chain of the inner membrane...

..The principle of protein oxidation in the IMS presumably has been conserved from the bacterial periplasm and has been adapted during evolution to drive the vectorial translocation of proteins from the cytosol into the mitochondria...

..As a consequence, the amount of cargo that can bind COPI might be important for the regulation of the vesicle flow in the early secretory pathway...

..The oxa2 sequence allowed the identification of a new subfamily of Oxa1/YidC/Alb3 proteins whose members appear to be ubiquitously present in mitochondria of fungi, plants, and animals including humans...

..Based on these observations, we propose Atp10p to be an Atp6p-specific chaperone that facilitates the incorporation of Atp6p into an intermediate subcomplex of ATPase subunits...

..Together, our data indicate that the Sec-independent function of YidC is conserved and essential for cell growth...

..Two of these pathways depend on the related inner membrane proteins Oxa1 and Cox18. A third route is less well defined and depends on the membrane-associated matrix protein Mba1...

..Since the Oxa1 monomer has a molecular weight of 43,000, our data suggest that the OXA translocase consists of a homooligomer most likely containing four Oxa1 subunits...

..pombe...

..These results suggest that although Tim23p is the main structural unit of the pore Tim17p is required for twin pore structure and provides the voltage gate for the TIM23 channel...

..Structural requirements for mitochondrial import were defined by site-directed mutagenesis. Our studies provide the prerequisite to understand the impact of specific mutations on the clinical phenotype of MCC deficiency...

..Such different properties presumably reflect diverse functions in vivo and might therefore explain why there are at least seven glutaredoxins in yeast...