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PMID: 19131594 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Function of mitochondrial Stat3 in cellular respiration.

Science (New York, N.Y.) ·Vol. 323 ·No. 5915 ·2009-02-06 ·Pages 793-7

Wegrzyn J, Potla R, Chwae YJ, Sepuri NB, Zhang Q, Koeck T, Derecka M, Szczepanek K, Szelag M, Gornicka A, Moh A, Moghaddas S, Chen Q, Bobbili S, Cichy J, Dulak J, Baker DP, Wolfman A, Stuehr D, Hassan MO, Fu XY, Avadhani N, Drake JI, Fawcett P, Lesnefsky EJ, Larner AC

Abstract

Cytokines such as interleukin-6 induce tyrosine and serine phosphorylation of Stat3 that results in activation of Stat3-responsive genes. We provide evidence that Stat3 is present in the mitochondria of cultured cells and primary tissues, including the liver and heart. In Stat3(-/-) cells, the activities of complexes I and II of the electron transport chain (ETC) were significantly decreased. We identified Stat3 mutants that selectively restored the protein's function as a transcription factor or its functions within the ETC. In mice that do not express Stat3 in the heart, there were also selective defects in the activities of complexes I and II of the ETC. These data indicate that Stat3 is required for optimal function of the ETC, which may allow it to orchestrate responses to cellular homeostasis.

MeSH Terms

Animals Cell Respiration Cells, Cultured Electron Transport Complex I/metabolism Electron Transport Complex II/metabolism Homeostasis Mice Mitochondria/metabolism Mitochondria, Heart/metabolism Mitochondria, Liver/metabolism Mitochondrial Membranes/metabolism NADH, NADPH Oxidoreductases/metabolism Oxidative Phosphorylation Phosphorylation Precursor Cells, B-Lymphoid/metabolism STAT3 Transcription Factor/chemistry,metabolism Serine/metabolism Signal Transduction

Chemicals

STAT3 Transcription Factor Stat3 protein, mouse Serine Electron Transport Complex II NADH, NADPH Oxidoreductases Grim19 protein, mouse Electron Transport Complex I

Authors & Affiliations

26 authors, click to expand affiliations / ORCID

Wegrzyn Joanna

Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.

Potla Ramesh

Chwae Yong-Joon

Sepuri Naresh B V

Zhang Qifang

Koeck Thomas

Derecka Marta

Szczepanek Karol

Szelag Magdalena

Gornicka Agnieszka

Moh Akira

Moghaddas Shadi

Chen Qun

Bobbili Santha

Cichy Joanna

Dulak Jozef

Baker Darren P

Wolfman Alan

Stuehr Dennis

Hassan Medhat O

Fu Xin-Yuan

Avadhani Narayan

Drake Jennifer I

Fawcett Paul

Lesnefsky Edward J

Larner Andrew C

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14 references, click to expand

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Article Info

Journal

Science (New York, N.Y.)

Abbr.

Science

ISSN

1095-9203

DOI

10.1126/science.1164551

Published

2009-02-06

Epub

2009-00-08

Pages

793-7

Language

English

Region

United States

NLM ID

0404511

PMCID

PMC2758306

Subset

Grants

NIAID NIH HHS · R01 AI059710 · United States

NCI NIH HHS · R01 CA098924-05 · United States

NCI NIH HHS · CA098924 · United States

NCI NIH HHS · R01 CA098924-04 · United States

NIAID NIH HHS · R01 AI059710-03 · United States

NCI NIH HHS · R01 CA098924-03 · United States

NIA NIH HHS · P01AG15885 · United States

NIAID NIH HHS · R01 AI059710-04 · United States

NCI NIH HHS · R01 CA098924 · United States

Corrections

CommentIn

PMID: 19197047

External Links

PubMed source DOI: 10.1126/science.1164551 PMC Full Text View journal details

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