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Mitochondrial Import Efficiency of ATFS-1 Regulates Mitochondrial UPR Activation
Open accessAbstract
Initiating Mitochondrial Repair: The mitochondrial unfolded protein response (UPRmt) mediates the up-regulation of nuclear encoded mitochondrial chaperone genes in response to mitochondrial dysfunction. How mitochondrial dysfunction is communicated to the nucleus is unclear, but requires the transcription factor, ATFS-1. Nargund et al. (p. 587 , published online 14 June) found that the key point of regulation in UPRmt signaling is mitochondrial protein import efficiency of ATFS-1. In addition to a nuclear localization sequence (NLS), ATFS-1 has a mitochondrial targeting sequence (MTS) that is necessary for UPRmt repression. ATFS-1 is normally imported efficiently into mitochondria and degraded by the Lon protease. However, in the presence of stress, some ATFS-1 fails to be imported into mitochondria and is trafficked to the nucleus. The juxtaposition of a C-terminal NLS to an N-terminal MTS in a transcriptional activator thus couples unfolded protein load in the mitochondrial matrix to a rectifying transcriptional response in the nucleus.
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Cites
Nakai, K., & Horton, P. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01336-x · Cited by 2,181
A mitochondrial specific stress response in mammalian cells
Zhao, Q., Wang, J., Levichkin, I. V., Stasinopoulos, S., Ryan, M. T., & Hoogenraad, N. J. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf445 · Cited by 1,026
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Metadata
- Authors
- Nargund, A. M., Pellegrino, M. W., Fiorese, C. J., Baker, B. M., & Haynes, C. M.
- Venue
- Science
- Published
- 2012-08-03
- Volume
- 337
- Issue
- 6094
- Pages
- 587-590
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1974522038
- Cited by
- 1,059
- References
- 2
- FWCI
- 17.43
- Type
- journal article
- Language
- en
- Open access
- green
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