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J. Biol. Chem. 288 (7): 4723-4732

© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

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

Prasad Tammineni{ddagger}2, Chandrashekhar Anugula{ddagger}1, Fareed Mohammed{ddagger}, Murari Anjaneyulu{ddagger}2, Andrew C. Larner§, , and Naresh Babu Venkata Sepuri{ddagger}3

From the {ddagger}Department of Biochemistry, University of Hyderabad, Hyderabad 500046, India and
the §Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298

ABSTRACT Back to Top

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.

Key Words: Cell Death • Mitochondria • Mitochondrial Transport • Molecular Chaperone • Protein translocation • ROS

Received for publication May 7, 2012. Revision received December 27, 2012.


1 Supported by a Indian Council of Medical Research for Junior Research Fellowship.

2 Supported by the Council of Scientific and Industrial Research.

3 To whom correspondence should be addressed. E-mail: nareshuohyd{at} or nbvssl{at}

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