2010
DOI: 10.1242/jcs.061846
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Sirtuin-3 deacetylation of cyclophilin D induces dissociation of hexokinase II from the mitochondria

Abstract: We demonstrate that the transition from a reliance on glycolysis to oxidative phosphorylation in a transformed cell line is dependent on an increase in the levels and activity of sirtuin-3. Sirtuin-3 deacetylates cyclophilin D, diminishing its peptidyl-prolyl cis-trans isomerase activity and inducing its dissociation from the adenine nucleotide translocator. Moreover, the sirtuin-3-induced inactivation of cyclophilin D causes a detachment of hexokinase II from the mitochondria that is necessary for stimulation… Show more

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Cited by 153 publications
(132 citation statements)
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“…29 Recently, SIRT3 has been shown to induce HKII detachment from OMM by deacetylating cyclophilin D, thereby increasing oxidative phosphorylation. 12 Our results demonstrate that under hypoxia SIRT3 overexpression causes a detachment of HKII from the mitochondria with a decrease in glycolytic rate and a reduction of lactate. Importantly, SIRT3 silencing increased both HKII binding to the mitochondrial fraction and lactate production.…”
Section: Discussionmentioning
confidence: 56%
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“…29 Recently, SIRT3 has been shown to induce HKII detachment from OMM by deacetylating cyclophilin D, thereby increasing oxidative phosphorylation. 12 Our results demonstrate that under hypoxia SIRT3 overexpression causes a detachment of HKII from the mitochondria with a decrease in glycolytic rate and a reduction of lactate. Importantly, SIRT3 silencing increased both HKII binding to the mitochondrial fraction and lactate production.…”
Section: Discussionmentioning
confidence: 56%
“…Our choice is motivated by the fact that SIRT3 has been shown to modulate HKII binding to the outer mitochondrial membrane (OMM), thereby regulating both the opening/closing of the permeability transition pore (PTP) and the glycolytic rate. 12,22 Figure 4a shows that hypoxia increased HKII expression. In fact, the decrease observed after 72 h of hypoxia in SIRT3-silenced cells is probably due to the increasing cell death rate.…”
Section: Resultsmentioning
confidence: 99%
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“…100,101 Interestingly, CyPD activity stabilizes mitoHK-II binding and forced dissociation of mitoHK-II leads to disruption of CyPD binding to ANT, suggesting a functional link between a stimulatory (CyPD) and an inhibitory (HK-II) molecule of the mPTP. 96,[102][103][104][105] It seems likely that the interaction between HK-II and CyPD is mediated by the previously mentioned VDAC/ANT interaction. 106,107 However, genetic evidence revealed that neither VDAC nor ANT is the main pore-forming component [108][109][110][111] and thus it is still not clear whether the indirect interaction of HK-II with CyPD plays a direct role in regulation of the mPTP.…”
Section: Pro-survival Effect Of Hk-iimentioning
confidence: 97%