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PMID:22700657

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Citation

Nargund, AM, Pellegrino, MW, Fiorese, CJ, Baker, BM and Haynes, CM (2012) Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337:587-90

Abstract

To better understand the response to mitochondrial dysfunction, we examined the mechanism by which ATFS-1 (activating transcription factor associated with stress-1) senses mitochondrial stress and communicates with the nucleus during the mitochondrial unfolded protein response (UPR(mt)) in Caenorhabditis elegans. We found that the key point of regulation is the mitochondrial import efficiency of ATFS-1. In addition to a nuclear localization sequence, ATFS-1 has an N-terminal mitochondrial targeting sequence that is essential for UPR(mt) repression. Normally, ATFS-1 is imported into mitochondria and degraded. However, during mitochondrial stress, we found that import efficiency was reduced, allowing a percentage of ATFS-1 to accumulate in the cytosol and traffic to the nucleus. Our results show that cells monitor mitochondrial import efficiency via ATFS-1 to coordinate the level of mitochondrial dysfunction with the protective transcriptional response.

Links

PubMed Online version:10.1126/science.1223560

Keywords

Active Transport, Cell Nucleus; Animals; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Nucleus/metabolism; Gene Expression Regulation; Mitochondria/metabolism; Nuclear Localization Signals/genetics; Nuclear Localization Signals/metabolism; Stress, Physiological; Transcription Factors/genetics; Transcription Factors/metabolism; Transcription, Genetic; Unfolded Protein Response

Significance

Annotations

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

CAEEL:LONM

involved_in

GO:0030163: protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:Q23272)

Seeded From UniProt

complete

CAEEL:O45278

involved_in

GO:0030150: protein import into mitochondrial matrix

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:TOM40

involved_in

GO:0030150: protein import into mitochondrial matrix

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ATFS1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ATFS1

involved_in

GO:0034514: mitochondrial unfolded protein response

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:ATFS1

located_in

GO:0005759: mitochondrial matrix

ECO:0000315: mutant phenotype evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:ATFS1

involved_in

GO:0010468: regulation of gene expression

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q86NC2

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:AFG3

involved_in

GO:0034982: mitochondrial protein processing

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q9XVQ2

involved_in

GO:0030150: protein import into mitochondrial matrix

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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