The Import of the Transcription Factor STAT3 into Mitochondria Depends on GRIM-19, a Component of the Electron Transport Chain

Abstract

The signal transducer and activator of transcription 3 (STAT3), a nuclear transcription factor, is also present in mitochondria and regulates cellular respiration in a transcriptional-independent manner. The mechanism of STAT3 import into mitochondria remains obscure. In this report we show that mitochondrial-localized STAT3 resides in the inner mitochondrial membrane. In vitro import studies show that the gene associated with retinoid interferon induced cell mortality 19 (GRIM-19), a complex I subunit that acts as a chaperone to recruit STAT3 into mitochondria. In addition, GRIM-19 enhances the integration of STAT3 into complex I. A S727A mutation in STAT3 reduces its import and assembly even in the presence of GRIM-19. Together, our studies unveil a novel chaperone function for GRIM-19 in the recruitment of STAT3 into mitochondria. Background: Apart from its mitochondrial localization, mechanistic details of STAT3 import and assembly in mitochondria remain elusive. Results: Using an in vitro import assay, we show that STAT3 associates with the mitochondrial inner membrane in a GRIM-19-dependent manner. Conclusion: GRIM-19 chaperones the recruitment of STAT3 into mitochondrial inner membrane complexes. Significance: This study identifies a novel function of GRIM-19 and a mechanism for STAT3 import into mitochondria.