2015
DOI: 10.2119/molmed.2015.00221
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Overexpression of Cystathionine γ-Lyase Suppresses Detrimental Effects of Spinocerebellar Ataxia Type 3

Abstract: Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine (polyQ) disorder caused by a CAG repeat expansion in the ataxin-3 (ATXN3) gene resulting in toxic protein aggregation. Inflammation and oxidative stress are considered secondary factors contributing to the progression of this neurodegenerative disease. There is no cure that halts or reverses the progressive neurodegeneration of SCA3. Here we show that overexpression of cystathionine γ-lyase, a central enzyme in cysteine metabolism, is protective in a Dros… Show more

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Cited by 40 publications
(38 citation statements)
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“…Moreover, CSE and CBS can also translocate into the mitochondria under various pathophysiological conditions [20,22]. Once in the mitochondrial compartment, H 2 S can stimulate mitochondrial function via a number of mechanisms outlined in the Introduction section [1835]. Based on the results of the current study, H 2 S, via S -sulfhydration of ATP synthase (Complex V), can also contribute to the activation of mitochondrial function.…”
Section: Discussionmentioning
confidence: 84%
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“…Moreover, CSE and CBS can also translocate into the mitochondria under various pathophysiological conditions [20,22]. Once in the mitochondrial compartment, H 2 S can stimulate mitochondrial function via a number of mechanisms outlined in the Introduction section [1835]. Based on the results of the current study, H 2 S, via S -sulfhydration of ATP synthase (Complex V), can also contribute to the activation of mitochondrial function.…”
Section: Discussionmentioning
confidence: 84%
“…It has been known for several decades high concentrations of H 2 S reversibly inhibit cytochrome c oxidase (complex IV) of the mitochondrial electron transport chain, resulting in the inhibition of ATP production and metabolic suppression [17]. However, an additional body of more recent data, which has emerged over the last decade, demonstrates that H 2 S, at lower concentrations, exerts a directionally different effect on mitochondria: it acts as a stimulator of mitochondrial bioenergetics and a mitochondrial protectant through a combination of several different mechanisms [1835]. First, H 2 S donates electrons to the mitochondrial electron transport chain through sulfide:quinone oxidoreductase (SQR) and mitochondrial Complex II, thereby stimulating oxidative phosphorylation (OXPHOS) and increasing mitochondrial ATP production [1827].…”
Section: Introductionmentioning
confidence: 99%
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“…There has been very little exploration of CSE levels in association with various disease states. Recently, CSE has been reported to be depleted in spinocerebellar-degeneration patients (30). In addition, glutathione and cysteine levels decline with normal aging (31,32) and in cancers (33).…”
Section: Discussionmentioning
confidence: 99%
“…In addition, it would help in understanding the spatio-temporal correlation of protein persulfidation with other oxPTM of cysteine in both health and disease. For example, we have recently observed a dramatic decrease of protein persulfidation in spinocerebellar ataxia 3 (SCA 3) 20 . This is a progressive neurodegenerative disease and could be reversed by overexpression of CSE, an intervention that also protects against tissue loss in the Drosophila SCA3 model 20 .…”
Section: Gaseous Signallingmentioning
confidence: 99%