A truncated progesterone receptor (PR-M) localizes to the mitochondrion and controls cellular respiration.

Qunsheng Dai, Anish A Shah, Rachana V Garde, Bryan A Yonish, Li Zhang, Neil A Medvitz, Sara E Miller, Elizabeth L Hansen, Carrie N Dunn, Thomas M Price

Molecular endocrinology (Baltimore, Md.) 2013 May

filter terms:

The cDNA for a novel truncated progesterone receptor (PR-M) was previously cloned from human adipose and aortic cDNA libraries. The predicted protein sequence contains 16 unique N-terminal amino acids, encoded by a sequence in the distal third intron of the progesterone receptor PR gene, followed by the same amino acid sequence encoded by exons 4 through 8 of the nuclear PR. Thus, PR-M lacks the N terminus A/B domains and the C domain for DNA binding, whereas containing the hinge and hormone-binding domains. In this report, we have localized PR-M to mitochondria using immunofluorescent localization of a PR-M-green fluorescent protein (GFP) fusion protein and in Western blot analyses of purified human heart mitochondrial protein. Removal of the putative N-terminal mitochondrial localization signal obviated association of PR-M with mitochondria, whereas addition of the mitochondrial localization signal to green fluorescent protein resulted in mitochondrial localization. Immunoelectron microscopy and Western blot analysis after mitochondrial fractionation identified PR-M in the outer mitochondrial membrane. Antibody specificity was shown by mass spectrometry identification of a PR peptide in a mitochondrial membrane protein isolation. Cell models of overexpression and gene silencing of PR-M demonstrated a progestin-induced increase in mitochondrial membrane potential and an increase in oxygen consumption consistent with an increase in cellular respiration. This is the first example of a truncated steroid receptor, lacking a DNA-binding domain that localizes to the mitochondrion and initiates direct non-nuclear progesterone action. We hypothesize that progesterone may directly affect cellular energy production to meet the increased metabolic demands of pregnancy.

Citation

Qunsheng Dai, Anish A Shah, Rachana V Garde, Bryan A Yonish, Li Zhang, Neil A Medvitz, Sara E Miller, Elizabeth L Hansen, Carrie N Dunn, Thomas M Price. A truncated progesterone receptor (PR-M) localizes to the mitochondrion and controls cellular respiration. Molecular endocrinology (Baltimore, Md.). 2013 May;27(5):741-53