Ethanol withdrawal hastens the aging of cytochrome c oxidase

Marianna E. Jung, Xiaohua Ju, Daniel B. Metzger, James W. Simpkins

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


We investigated whether abrupt ethanol withdrawal (EW) age-specifically inhibits a key mitochondrial enzyme, cytochrome c oxidase (COX), and whether estrogen mitigates this problem. We also tested whether this possible effect of EW involves a substrate (cytochrome c) deficiency that is associated with proapoptotic Bcl2-associated X protein (BAX) and mitochondrial membrane swelling. Ovariectomized young, middle age, and older rats, with or without 17β-estradiol (E2) implantation, underwent repeated EW. Cerebelli were collected to measure COX activity and the mitochondrial membrane swelling using spectrophotometry and the mitochondrial levels of cytochrome c and BAX using an immunoblot method. The loss of COX activity and the mitochondrial membrane swelling occurred only in older rats under control diet conditions but occurred earlier, starting in the young rats under EW conditions. E2 treatment mitigated these EW effects. EW increased mitochondrial BAX particularly in middle age rats but did not alter cytochrome c. Collectively EW hastens but E2 delays the age-associated loss of COX activity. This EW effect is independent of cytochrome c but may involve the mitochondrial overload of BAX and membrane vulnerability.

Original languageEnglish
Pages (from-to)618.e21-618.e32
JournalNeurobiology of Aging
Issue number3
StatePublished - Mar 2012


  • 17β-estradiol
  • Age
  • BAX (Bcl2-associated X protein)
  • Brain aging
  • Cytochrome c
  • Cytochrome c oxidase
  • Ethanol withdrawal
  • Female rats
  • Mitochondria
  • Mitochondrial membrane swelling
  • Mitochondrial respiration


Dive into the research topics of 'Ethanol withdrawal hastens the aging of cytochrome c oxidase'. Together they form a unique fingerprint.

Cite this