論文

査読有り 国際誌
2015年12月

The ubiquitin-proteasome system and autophagy are defective in the taurine-deficient heart.

Amino acids
  • Chian Ju Jong
  • ,
  • Takashi Ito
  • ,
  • Stephen W Schaffer

47
12
開始ページ
2609
終了ページ
22
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00726-015-2053-7

Taurine depletion leads to impaired mitochondrial function, as characterized by reduced ATP production and elevated superoxide generation. These defects can fundamentally alter cardiomyocyte function and if left unchanged can result in cell death. To protect against these stresses, cardiomyocytes possess quality control processes, such as the ubiquitin-proteasome system (UPS) and autophagy, which can rejuvenate cells through the degradation of damaged proteins and organelles. Hence, the present study tested the hypothesis that reactive oxygen species generated by damaged mitochondria initiates UPS and autophagy in the taurine-deficient heart. Using transgenic mice lacking the taurine transporter (TauTKO) as a model of taurine deficiency, it was shown that the levels of ubiquitinated protein were elevated, an effect associated with a decrease in ATP-dependent 26S β5 proteasome activity. Treating the TauTKO mouse with the mitochondria-specific antioxidant, mitoTEMPO, largely abolished the increase in ubiquitinated protein content. The TauTKO heart was also associated with impaired autophagy, characterized by an increase in the initiator, Beclin-1, and autophagosome content, but a defect in the generation of active autophagolysosomes. Although mitoTEMPO treatment only restores the oxidative balance within the mitochondria, it appeared to completely disrupt the crosstalk between the damaged mitochondria and the quality control processes. Thus, mitochondrial oxidative stress is the main trigger initiating the quality control systems in the taurine-deficient heart. We conclude that the activation of the UPS and autophagy is another fundamental function of mitochondria.

リンク情報
DOI
https://doi.org/10.1007/s00726-015-2053-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26193770
ID情報
  • DOI : 10.1007/s00726-015-2053-7
  • PubMed ID : 26193770

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