The import of superoxide dismutase-2 (SOD2) into mitochondria is vital for the survival of eukaryotic cells. SOD2 is encoded within the nuclear genome and translocated into mitochondria for activation after translation in the cytosol. The molecular chaperone Hsp70 modulates SOD2 activity by promoting import of SOD2 into mitochondria. In turn, the activity of Hsp70 is controlled by co-chaperones, particularly CHIP, which directs Hsp70-bound proteins for degradation in the proteasomes. We investigated the mechanisms controlling the activity of SOD2 to signal activation and maintain mitochondrial redox balance. We demonstrate that Akt1 binds to and phosphorylates the C terminus of Hsp70 on Serine631, which inhibits CHIP-mediated SOD2 degradation thereby stabilizing and promoting SOD2 import. Conversely, increased mitochondrial-H2O2 formation disrupts Akt1-mediated phosphorylation of Hsp70, and non-phosphorylatable Hsp70 mutants decrease SOD2 import, resulting in mitochondrial oxidative stress. Our findings identify Hsp70 phosphorylation as a physiological mechanism essential for regulation of mitochondrial redox balance.
Pubmed ID: 30485823 RIS Download
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This polyclonal targets PPP2CA, PPP2CB, PPP4C
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View all literature mentionsMus musculus with name B6.129S4(FVB)-Akt1tm2.2Mbb/J from IMSR.
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View all literature mentionsThis unknown targets p38 MAPK Isoform Activation Sampler Kit
View all literature mentionsThis monoclonal targets AKT
View all literature mentionsThis polyclonal targets PPM1A, PPM1B
View all literature mentionsThis polyclonal targets PPP2CA, PPP2CB, PPP4C
View all literature mentionsThis polyclonal targets STUB1
View all literature mentionsThis polyclonal targets AKT (phospho Thr308)
View all literature mentions