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Amino Acids

, Volume 47, Issue 12, pp 2609–2622 | Cite as

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

  • Chian Ju Jong
  • Takashi Ito
  • Stephen W. SchafferEmail author
Original Article

Abstract

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.

Keywords

Proteasome activity Taurine deficiency Autophagosome formation Mitochondrial morphology Consequences of mitochondrial oxidative stress Protein degradation Defective autophagolysosome 

Notes

Compliance with ethical standards

Conflict of interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Chian Ju Jong
    • 1
  • Takashi Ito
    • 2
  • Stephen W. Schaffer
    • 1
    Email author
  1. 1.Department of PharmacologyUniversity of South Alabama College of MedicineMobileUSA
  2. 2.School of PharmacyHyogo University of Health SciencesKobeJapan

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