Function of mitochondrial Stat3 in cellular respiration.
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.
Wegrzyn
Joanna
J
Department of Biochemistry and Molecular Biology and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA.
Potla
Ramesh
R
Chwae
Yong-Joon
YJ
Sepuri
Naresh B V
NB
Zhang
Qifang
Q
Koeck
Thomas
T
Derecka
Marta
M
Szczepanek
Karol
K
Szelag
Magdalena
M
Gornicka
Agnieszka
A
Moh
Akira
A
Moghaddas
Shadi
S
Chen
Qun
Q
Bobbili
Santha
S
Cichy
Joanna
J
Dulak
Jozef
J
Baker
Darren P
DP
Wolfman
Alan
A
Stuehr
Dennis
D
Hassan
Medhat O
MO
Fu
Xin-Yuan
XY
Avadhani
Narayan
N
Drake
Jennifer I
JI
Fawcett
Paul
P
Lesnefsky
Edward J
EJ
Larner
Andrew C
AC
D000818:Animals; D019069:Cell Respiration; D002478:Cells, Cultured; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D006706:Homeostasis; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D054448:Precursor Cells, B-Lymphoid / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D012694:Serine; D042963:Electron Transport Complex II; D009247:NADH, NADPH Oxidoreductases; C486684:Grim19 protein, mouse; D042967:Electron Transport Complex I