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Mol Cell. 2015 Apr 2;58(1):123-33. doi: 10.1016/j.molcel.2015.02.008. Epub 2015 Mar 12.

Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt).

Author information

1
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
2
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Medical College, New York, NY 10065, USA.
3
Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: haynesc@mskcc.org.

Abstract

Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to-nuclear communication during the mitochondrial UPR, via ChIP-sequencing. Surprisingly, in addition to regulating mitochondrial chaperone, OXPHOS complex assembly factor, and glycolysis genes, ATFS-1 bound directly to OXPHOS gene promoters in both the nuclear and mitochondrial genomes. Interestingly, atfs-1 was required to limit the accumulation of OXPHOS transcripts during mitochondrial stress, which required accumulation of ATFS-1 in the nucleus and mitochondria. Because balanced ATFS-1 accumulation promoted OXPHOS complex assembly and function, our data suggest that ATFS-1 stimulates respiratory recovery by fine-tuning OXPHOS expression to match the capacity of the suboptimal protein-folding environment in stressed mitochondria, while simultaneously increasing proteostasis capacity.

PMID:
25773600
PMCID:
PMC4385436
DOI:
10.1016/j.molcel.2015.02.008
[Indexed for MEDLINE]
Free PMC Article

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