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Sci. Signal., 7 August 2012
Vol. 5, Issue 236, p. ec208
[DOI: 10.1126/scisignal.2003468]


Cell Biology Initiating Mitochondrial Repair

Stella M. Hurtley

Science, AAAS, Cambridge CB2 1LQ, UK

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. 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.

A. M. Nargund, M. W. Pellegrino, C. J. Fiorese, B. M. Baker, C. M. Haynes, Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337, 587–590 (2012). [Abstract] [Full Text]

Citation: S. M. Hurtley, Initiating Mitochondrial Repair. Sci. Signal. 5, ec208 (2012).

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