Acetyl CoA Carboxylase Inactivation and Meiotic Maturation in Mouse Oocytes

Authors

Deepa S. Valsangkar, Marquette University
Stephen Downs, Marquette UniversityFollow

Document Type

Article

Language

eng

Format of Original

14 p.

Publication Date

9-2015

Publisher

Wiley

Source Publication

Molecular Reproduction and Development

Source ISSN

1040-452X

Original Item ID

doi: 10.1002/mrd.22505

Abstract

In mouse oocytes, meiotic induction by pharmacological activation of PRKA (adenosine monophosphate-activated protein kinase; formerly known as AMPK) or by hormones depends on stimulation of fatty acid oxidation (FAO). PRKA stimulates FAO by phosphorylating and inactivating acetyl CoA carboxylase (ACAC; formerly ACC), leading to decreased malonyl CoA levels and augmenting fatty-acid transport into mitochondria. We investigated a role for ACAC inactivation in meiotic resumption by testing the effect of two ACAC inhibitors, CP-640186 and Soraphen A, on mouse oocytes maintained in meiotic arrest in vitro. These inhibitors significantly stimulated the resumption of meiosis in arrested cumulus cell-enclosed oocytes, denuded oocytes, and follicle-enclosed oocytes. This stimulation was accompanied by an increase in FAO. Etomoxir, a malonyl CoA analogue, prevented meiotic resumption as well as the increase in FAO induced by ACAC inhibition. Citrate, an ACAC activator, and CBM-301106, an inhibitor of malonyl CoA decarboxylase, which converts malonyl CoA to acetyl CoA, suppressed both meiotic induction and FAO induced by follicle-stimulating hormone, presumably by maintaining elevated malonyl CoA levels. Mouse oocyte-cumulus cell complexes contain both isoforms of ACAC (ACACA and ACACB); when wild-type and Acacb^−/− oocytes characteristics were compared, we found that these single-knockout oocytes showed a significantly higher FAO level and a reduced ability to maintain meiotic arrest, resulting in higher rates of germinal vesicle breakdown. Collectively, these data support the model that ACAC inactivation contributes to the maturation-promoting activity of PRKA through stimulation of FAO.

Comments

Accepted version. Molecular Reproduction and Development, Vol. 82, No. 9 (September 2015): 679-693. DOI. © 2015 Wiley. Used with permission.

Recommended Citation

Valsangkar, Deepa S. and Downs, Stephen, "Acetyl CoA Carboxylase Inactivation and Meiotic Maturation in Mouse Oocytes" (2015). Biological Sciences Faculty Research and Publications. 497.
https://epublications.marquette.edu/bio_fac/497