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Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins.

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TLDR
The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes.
Abstract
Mitochondria import nuclear-encoded precursor proteins to four different subcompartments. Specific import machineries have been identified that direct the precursor proteins to the mitochondrial outer membrane, inner membrane or matrix, respectively. However, a machinery dedicated to the import of mitochondrial intermembrane space (IMS) proteins has not been found so far. We have identified the essential IMS protein Mia40 (encoded by the Saccharomyces cerevisiae open reading frame YKL195w). Mitochondria with a mutant form of Mia40 are selectively inhibited in the import of several small IMS proteins, including the essential proteins Tim9 and Tim10. The import of proteins to the other mitochondrial subcompartments does not depend on functional Mia40. The binding of small Tim proteins to Mia40 is crucial for their transport across the outer membrane and represents an initial step in their assembly into IMS complexes. We conclude that Mia40 is a central component of the protein import and assembly machinery of the mitochondrial IMS.

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Journal ArticleDOI

Translocation of proteins into mitochondria.

TL;DR: 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.
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Importing Mitochondrial Proteins: Machineries and Mechanisms

TL;DR: Recent insights into the importing and sorting of mitochondrial proteins and their contributions to mitochondrial biogenesis are discussed.
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Mitochondrial protein import: from proteomics to functional mechanisms

TL;DR: This work has shown that protein translocases do not function as independent units but are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum.
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Mitochondrial Machineries for Protein Import and Assembly.

TL;DR: The versatility and dynamic organization of the mitochondrial protein import machineries are discussed, which are crucial for understanding the integration of protein translocases into a large network that controls organelle biogenesis, function, and dynamics.
Journal ArticleDOI

A disulfide relay system in the intermembrane space of mitochondria that mediates protein import.

TL;DR: It is suggested that the existence of a disulfide exchange system in the IMS is unexpected in view of the free exchange of metabolites between IMS and cytosol via porin channels, and reflects the evolutionary origin of the I MS from the periplasmic space of the prokaryotic ancestors of mitochondria.
References
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TL;DR: A series of yeast shuttle vectors and host strains has been created to allow more efficient manipulation of DNA in Saccharomyces cerevisiae to perform most standard DNA manipulations in the same plasmid that is introduced into yeast.
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Journal ArticleDOI

The proteome of Saccharomyces cerevisiae mitochondria

TL;DR: The mitochondrial proteome will provide an important database for the analysis of new mitochondrial and mitochondria-associated functions and the characterization of mitochondrial diseases.
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