Function of mitochondrial Stat3 in cellular respiration (Sciencexpress, 2009, doi:10.1126/science.1164551)

報告日期: 2009/05/12
報告時間: 15:10/16:00
報告學生: 王佩文
講評老師: 蘇五洲
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980512-1.pdf

Function of mitochondrial Stat3 in cellular respiration

Wegrzyn J, Potla R, Chwae YJ, et al

Science 323:793-7, 2009

 

Date: 2009/05/12

Speaker: 王佩文

Commentator: 蘇五洲 教授

Place: Room 602

 

ABSTRACT

Signal transducers and activators of transcription (STATs) regulate gene expression in the nucleus in response to cell surface receptors that are activated by cytokines. Stat3 proteins represent the canonical mediators of signals elicited by type I cytokine receptors at the cell surface. The binding of a cytokine to its receptor triggers an intracellular cascade of events, beginning with the activation of an enzyme, Jak kinase, which is associated with the receptor’s cytoplasmic domain. The activated receptor-Jak complex then recruits and phosphorylates a tyrosine residue in cognate STAT proteins. This modification causes the STAT protein to relocate to the nucleus, where, as a dimer, it binds to specific DNA sequences and promotes gene expression.(Schindler, Levy et al. 2007) GRIM-19, a mitochondrial protein, was purified as a component of complex I of the electron transport chain (ETC) and demonstrated that interacts with Stat3 and inhibits Stat3 transcriptional activity. This paper investigated the potential mitochondrial location of Stat3, revealing that a fraction of cellular Stat3 resides within the mitochondria of mouse myocytes and hepatocytes and provides evidence that Stat3 associates with GRIM-19–containing complexes I and II, which are components of the ETC that generates energy by oxidative phosphorylation of cultured cells and primary tissues including liver and heart. In a subset of mouse B lymphocytes (proB cell) devoid of Stat3, oxidative phosphorylation was reduced, a defect attributable to the diminished activity of complexes I and II. The expression of Stat3 in these otherwise Stat3-null cells restored oxidative phosphorylation, and this rescue of mitochondrial function did not require the DNA binding domain, the dimerization motif, or the tyrosine phosphorylation site that controls Stat3 nuclear localization and transcriptional activity, consistent with a transcription-independent role for Stat3. These data indicate that Stat3 is required for optimal function of the ETC which may allow it to orchestrate responses to cellular homeostasis.(Myers 2009)

 

REFERENCE

Myers, M. G., Jr. (2009). "Cell biology. Moonlighting in mitochondria." Science 323(5915): 723-4.

Schindler, C., D. E. Levy, et al. (2007). "JAK-STAT signaling: from interferons to cytokines." J Biol Chem 282(28): 20059-63.