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PMID:22993211

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Citation

Schreiner, B, Westerburg, H, Forné, I, Imhof, A, Neupert, W and Mokranjac, D' (2012) Role of the AAA protease Yme1 in folding of proteins in the intermembrane space of mitochondria. Mol. Biol. Cell '

Abstract

The vast majority of mitochondrial proteins are synthesized in the cytosol and transported into the organelle in a largely, if not completely, unfolded state. The proper function of mitochondria thus depends on folding of several hundreds of proteins in the various subcompartments of the organelle. Whereas folding of proteins in the mitochondrial matrix is supported by members of several chaperone families, very little is known about folding of proteins in the intermembrane space (IMS). We targeted dihydrofolate reductase (DHFR), as a model substrate, to the IMS of yeast mitochondria and analyzed its folding. DHFR can fold in this compartment and its aggregation upon heat shock can be prevented in an ATP-dependent manner. Yme1, a AAA protease of the IMS, prevented aggregation of DHFR. Analysis of protein aggregates in mitochondria lacking Yme1 revealed the presence of a number of proteins that are involved in the establishment of mitochondrial ultrastructure, lipid metabolism, protein import and respiratory growth. These findings explain the pleiotropic effects of deletion of YME1 and suggest an important role of Yme1 in the proteostasis of mitochondria by assisting in protein folding, in addition to its proteolytic activity.

Links

PubMed Online version:10.1091/mbc.E12-05-0420

Keywords


Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

YEAST:MGR1

involved_in

GO:0045041: protein import into mitochondrial intermembrane space

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete

YEAST:YME1

involved_in

GO:0006457: protein folding

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

YEAST:YME1

involved_in

GO:0045041: protein import into mitochondrial intermembrane space

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete

YEAST:MPM1

located_in

GO:0005758: mitochondrial intermembrane space

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

YEAST:MGR3

involved_in

GO:0045041: protein import into mitochondrial intermembrane space

ECO:0005547: biological system reconstruction evidence based on inference from background scientific knowledge used in manual assertion

P

Seeded From UniProt

complete


See also

References

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