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Publication : A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome integrity.

First Author  Seibenhener ML Year  2013
Journal  Biochim Biophys Acta Volume  1833
Issue  3 Pages  452-9
PubMed ID  23147249 Mgi Jnum  J:198840
Mgi Id  MGI:5499282 Doi  10.1016/j.bbamcr.2012.11.004
Citation  Seibenhener ML, et al. (2013) A role for sequestosome 1/p62 in mitochondrial dynamics, import and genome integrity. Biochim Biophys Acta 1833(3):452-9
abstractText  As a signaling scaffold, p62/sequestosome (p62/SQSTM1) plays important roles in cell signaling and degradation of misfolded proteins. While localization of p62 to mitochondria has been reported, a description of its function once there, remains unclear. Here, we report that p62 is localized to mitochondria in non-stressed situations and demonstrate that deficiency in p62 exacerbates defects in mitochondrial membrane potential and energetics leading to mitochondrial dysfunction. We report on the relationship between mitochondrial protein import and p62. In a p62 null background, mitochondrial import of the mitochondrial transcription factor TFAM is disrupted. When p62 is returned, mitochondrial function is restored to more normal levels. We identify for the first time that p62 localization plays a role in regulating mitochondrial morphology, genome integrity and mitochondrial import of a key transcription factor. We present evidence that these responses to the presence of p62 extend beyond the protein's immediate influence on membrane potential.
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