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Nutrients. 2017 Jul 25;9(8). pii: E795. doi: 10.3390/nu9080795.

Role of Mitochondria and Endoplasmic Reticulum in Taurine-Deficiency-Mediated Apoptosis.

Author information

1
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA. cjjong84@gmail.com.
2
Faculty of Biotechnology, Fukui Prefectural University, Fukui 910-1195, Japan. tito@fpu.ac.jp.
3
Program in Integrative Biology and Center for Complex Systems and Brain Sciences, College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA. hprentic@health.fau.edu.
4
Program in Integrative Biology and Center for Complex Systems and Brain Sciences, College of Medicine, Florida Atlantic University, Boca Raton, FL 33431, USA. jwu@health.fau.edu.
5
Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL 36688, USA. sschaffe@southalabama.edu.

Abstract

Taurine is a ubiquitous sulfur-containing amino acid found in high concentration in most tissues. Because of its involvement in fundamental physiological functions, such as regulating respiratory chain activity, modulating cation transport, controlling inflammation, altering protein phosphorylation and prolonging lifespan, taurine is an important nutrient whose deficiency leads to severe pathology and cell death. However, the mechanism by which taurine deficiency causes cell death is inadequately understood. Therefore, the present study examined the hypothesis that overproduction of reactive oxygen species (ROS) by complex I of the respiratory chain triggers mitochondria-dependent apoptosis in hearts of taurine transporter knockout (TauTKO) mice. In support of the hypothesis, a 60% decrease in mitochondrial taurine content of 3-month-old TauTKO hearts was observed, which was associated with diminished complex I activity and the onset of mitochondrial oxidative stress. Oxidative damage to stressed mitochondria led to activation of a caspase cascade, with stimulation of caspases 9 and 3 prevented by treatment of 3-month-old TauTKO mice with the mitochondria specific antioxidant, MitoTempo. In 12 month-old, but not 3-month-old, TauTKO hearts, caspase 12 activation contributes to cell death, revealing a pathological role for endoplasmic reticulum (ER) stress in taurine deficient, aging mice. Thus, taurine is a cytoprotective nutrient that ensures normal mitochondrial and ER function, which is important for the reduction of risk for apoptosis and premature death.

KEYWORDS:

apoptosis; caspase cascade; endoplasmic reticulum stress; mitochondria; mitochondria encoded proteins; oxidative stress; respiratory chain; tRNALeu(UUR)

PMID:
28757580
PMCID:
PMC5579589
DOI:
10.3390/nu9080795
[Indexed for MEDLINE]
Free PMC Article

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