The transcription factor ATF5 mediates a mammalian mitochondrial UPR Journal Article


Authors: Fiorese, C. J.; Schulz, A. M.; Lin, Y. F.; Rosin, N.; Pellegrino, M. W.; Haynes, C. M.
Article Title: The transcription factor ATF5 mediates a mammalian mitochondrial UPR
Abstract: Mitochondrial dysfunction is pervasive in human pathologies such as neurodegeneration, diabetes, cancer, and pathogen infections as well as during normal aging. Cells sense and respond to mitochondrial dysfunction by activating a protective transcriptional program known as the mitochondrial unfolded protein response (UPRmt), which includes genes that promote mitochondrial protein homeostasis and the recovery of defective organelles [1, 2]. Work in Caenorhabditis elegans has shown that the UPRmt is regulated by the transcription factor ATFS-1, which is regulated by organelle partitioning. Normally, ATFS-1 accumulates within mitochondria, but during respiratory chain dysfunction, high levels of reactive oxygen species (ROS), or mitochondrial protein folding stress, a percentage of ATFS-1 accumulates in the cytosol and traffics to the nucleus where it activates the UPRmt [2]. While similar transcriptional responses have been described in mammals [3, 4], how the UPRmt is regulated remains unclear. Here, we describe a mammalian transcription factor, ATF5, which is regulated similarly to ATFS-1 and induces a similar transcriptional response. ATF5 expression can rescue UPRmt signaling in atfs-1-deficient worms requiring the same UPRmt promoter element identified in C. elegans. Furthermore, mammalian cells require ATF5 to maintain mitochondrial activity during mitochondrial stress and promote organelle recovery. Combined, these data suggest that regulation of the UPRmt is conserved from worms to mammals. © 2016 Elsevier Ltd
Journal Title: Current Biology
Volume: 26
Issue: 15
ISSN: 0960-9822
Publisher: Cell Press  
Date Published: 2016-08-08
Start Page: 2037
End Page: 2043
Language: English
DOI: 10.1016/j.cub.2016.06.002
PROVIDER: scopus
PMCID: PMC4980197
PUBMED: 27426517
DOI/URL:
Notes: Article -- Export Date: 1 November 2016 -- Source: Scopus
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MSK Authors
  1. Cole Haynes
    24 Haynes
  2. Yi-Fan Lin
    4 Lin
  3. Anna Mareike Schulz
    4 Schulz
  4. Nadine   Rosin
    1 Rosin