4.5 Article Retracted Publication

被撤回的出版物: Ethanol sensitizes mitochondria to the permeability transition by inhibiting deacetylation of cyclophilin-D mediated by sirtuin-3 (Publication with Expression of Concern. See vol. 129, pg. 869, 2016) (Retracted article. See vol. 129, pg. 2685, 2016)

Journal

JOURNAL OF CELL SCIENCE
Volume 123, Issue 23, Pages 4117-4127

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.073502

Keywords

Sirtuin-3; Ethanol; Mitochondria; Cyclophilin-D

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Funding

  1. National Institutes of Health [R01AA012897]

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Ethanol increases the vulnerability of mitochondria to induction of the mitochondrial permeability transition (MPT). Cyclophilin-D activity enhances the potential for the permeability transition pore (PTP) to open. In the present study, we demonstrate that ethanol and its metabolism sensitize the PTP to opening, in part by increasing the acetylation and activity of cyclophilin-D. This effect of ethanol is mediated by inhibiting the activity of sirtuin-3, an NAD(+) dependent deacetylase that is localized to the mitochondrial matrix. The ethanol-enhanced acetylation of cyclophilin-D also increases the interaction of cyclophilin-D with the adenine nucleotide translocator-1 (ANT-1) and is dependent on ethanol metabolism. Moreover, activation of AMPK, a known positive modulator of sirtuin activity, prevented the ethanol-induced suppression of sirtuin-3 activity and the attendant increase of cyclophilin-D acetylation, activity and association with ANT-1. Additionally, AMPK reactivation of sirtuin-3 prevented the sensitization to the MPT and the enhancement of cell killing by TNF in cells exposed to ethanol.

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