Aromatase deficiency inhibits the permeability transition in mouse liver mitochondria

Loredana Moro, Arnaldo A. Arbini, Jer Tsong Hsieh, Jeffery Ford, Evan R. Simpson, Asghar Hajibeigi, Orhan K. Öz

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Lack of estrogens affects male physiology in a number of ways, including severe changes in liver metabolism that result in lipid accumulation and massive hepatic steatosis. Here we investigated whether estrogen deficiency may alter the functionality and permeability properties of liver mitochondria using, as an experimental model, aromatase knockout (ArKO) male mice, which cannot synthesize endogenous estrogens due to a disruption of the Cyp19 gene. Liver mitochondria isolated from ArKO mice displayed increased activity of the mitochondrial respiratory complex IV compared with wild-type mice and were less prone to undergo cyclosporin A-sensitive mitochondrial permeability transition (MPT) induced by calcium loading.Thealtered permeability properties of the mitochondrial membranes were not due to changes in reactive oxygen species, ATP levels, or mitochondrial membrane potential but were associated with increased content of the phospholipid cardiolipin, structural component of the mitochondrial membranes and regulator of the MPT pore, and with increased mitochondrial protein levels of Bcl-2 and the adenine nucleotide translocator (ANT), regulator and component of the MPT pore, respectively. Real-time RT-PCR demonstrated increased mRNA levels for Bcl-2 and ANT2 but not for the ANT1 isoform in ArKO livers. Supplementation of 17β-estradiol retrieved ArKO mice from massive hepatic steatosis and restored mitochondrial permeability properties, cardiolipin, Bcl-2, and ANT2 levels. Overall, our findings demonstrate an important role of estrogens in the modulation of hepatic mitochondrial function and permeability properties in males and suggest that estrogen deficiency may represent a novel positive regulator of Bcl-2 and ANT2 proteins, two inhibitors of MPT occurrence and powerful antiapoptotic molecules.

Original languageEnglish (US)
Pages (from-to)1643-1652
Number of pages10
JournalEndocrinology
Volume151
Issue number4
DOIs
StatePublished - Apr 1 2010

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Aromatase deficiency inhibits the permeability transition in mouse liver mitochondria'. Together they form a unique fingerprint.

  • Cite this