Mitochondrial glutathione

Kulinsky, V. I.; Kolesnichenko, L. S.

doi:10.1134/s0006297907070024

Cited by 19 publications

(20 citation statements)

References 30 publications

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“…Given the well-established role of mGSH in multiple aspects of mitochondrial antioxidant defense (27) and the lack of GSH-synthetic machinery inside mitochondria (16), it was surprising that the significance of GSH-transporting mechanisms and the consequence of their deficiencies in the brain had never been studied before. The current study therefore represents the first attempt in addressing these fundamental issues.…”

Section: Discussionmentioning

confidence: 99%

Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria

Kamga

Zhang

Wang

2010

American Journal of Physiology-Cell Physiology

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Glutathione transport into mitochondria is mediated by oxoglutarate (OGC) and dicarboxylate carrier (DIC) in the kidney and liver. However, transport mechanisms in brain mitochondria are unknown. We found that both carriers were expressed in the brain. Using cortical mitochondria incubated with physiological levels of glutathione, we found that butylmalonate, a DIC inhibitor, reduced mitochondrial glutathione to levels similar to those seen in mitochondria incubated without extramitochondrial glutathione (59% of control). In contrast, phenylsuccinate, an OGC inhibitor, had no effect (97% of control). Additional experiments with DIC and OGC short hairpin RNA in neuronal-like PC12 cells resulted in similar findings. Significantly, DIC inhibition resulted in increased reactive oxygen species (ROS) content in and H(2)O(2) release from mitochondria. It also led to decreased membrane potential, increased basal respiration rates, and decreased phosphorus-to-oxygen (P/O) ratios, especially when electron transport was initiated from complex I. Accordingly, we found that DIC inhibition impaired complex I activity, but not those for complexes II and III. This impairment was not associated with dislodgment of complex subunits. These results suggest that DIC is the main glutathione transporter in cortical mitochondria and that DIC-mediated glutathione transport is essential for these mitochondria to maintain ROS homeostasis and normal respiratory functions.

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Section: Discussionmentioning

confidence: 99%

Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria

Kamga

Zhang

Wang

2010

American Journal of Physiology-Cell Physiology

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“…Notably, glutathione is synthesized in the cytosol and it is transported into organelles via glutathione transferases. Mitochondrial glutathione is 10–15% of the total cellular glutathione, but its concentration is similar to the cytosolic one (5–10 mM in rat liver) [116]. …”

Section: Local Ros Signaling: Sources Targets and Mediatorsmentioning

confidence: 99%

“…Via metabolizing lipid hydroperoxides (e.g. cardiolipin hydroperoxide in the mitochondria) and counteracting with lypoxygenases as well as cyclooxygenase, GPx4 exerts anti-inflammatory and anti-apoptotic actions [116, 136]. Trx and Grx are also important modulators in the glutathione-dependent redox signaling as they regulate the duration and degree of reversible S-glutathionylation of target signaling molecules [115, 116].…”

Section: Local Ros Signaling: Sources Targets and Mediatorsmentioning

confidence: 99%

SR/ER–mitochondrial local communication: Calcium and ROS

Csordás

Hajnóczky

2009

Biochimica et Biophysica Acta (BBA) - Bioenergetics

267

199

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Mitochondria form junctions with the sarco/endoplasmic reticulum (SR/ER), which support signal transduction and biosynthetic pathways and affect organellar distribution. Recently, these junctions have received attention because of their pivotal role in mediating calcium signal propagation to the mitochondria, which is important for both ATP production and mitochondrial cell death. Many of the SR/ER-mitochondrial calcium transporters and signaling proteins are sensitive to redox regulation and are directly exposed to the reactive oxygen species (ROS) produced in the mitochondria and SR/ER. Although ROS has been emerging as a novel signaling entity, the redox signaling of the SR/ER-mitochondrial interface is yet to be elucidated. We describe here possible mechanisms of the mutual interaction between local Ca2+ and ROS signaling in the control of SR/ER-mitochondrial function.

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“…French scientists have continuously used the term hormonology to denote the biological aspects of the discipline, reserving the term endocrinology for the medical specialty. In 1997, Russian scientists also adopted this term (Kulinskii & Kolesnichenko 1997).…”

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confidence: 99%

Hormonology: a genomic perspective on hormonal research

Hsueh

Bouchard²,

Ben‐Shlomo³

2005

Journal of Endocrinology

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Recent advances in comparative genomics allow a new paradigm for hormonal research. At the centennial of the first use of the term hormone by Ernest Starling, we reflected on the changing approaches in elucidating hormonal signaling mechanisms and highlighted the inadequacy of the term endocrinology, implying remote activation, to describe the diverse modes of hormone actions. Several examples were presented to underscore the power of comparative genomics in the identification of new polypeptide hormones, receptors, and signaling pathways. We propose the use of the term hormonology to more accurately reflect the expanding boundaries of the discipline.

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Mitochondrial glutathione

Abstract: Many functions of mitochondrial GSH are significantly different from those of cytosolic GSH. This review considers the peculiarity of functions of mitochondrial GSH and enzymes of its metabolism, especially glutathione peroxidase 4, glutaredoxin 2, and kappa-glutathione transferase.

Cited by 19 publications

References 30 publications

Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria

Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria

SR/ER–mitochondrial local communication: Calcium and ROS

Hormonology: a genomic perspective on hormonal research

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