Finally, the availability of acetyl units for biosynthetic purposes was evaluated as histone acetylation and VDR silencing also decreased this process, which was measured as histone H4 acetylation. Collectively, these observations indicate that upon VDR silencing, the increased respiratory chain activity oxidizes metabolic intermediates, preventing their utilization in biosynthetic pathways. We demonstrated the exemplary diversion of acetyl-CoA, the incorporation of which is reduced during cholesterol biosynthesis, prenylation events and histone remodeling. Hormonal stimulus affects the transcription of mitochondrially encoded OXPHOS both indirectly, by inducing nuclear signals, and directly, by localizing in the organelle and interacting with response elements in PR-171 mitochondrial DNA. To date, VDR function in the mitochondria BIBW2992 remains uncharacterized. In the present study, we demonstrated that the VDR promotes proliferation, as its silencing strongly affects the growth rate of HaCaT and other cancer cell lines expressing a mitochondrial VDR. Starting with the previously characterized HaCaT cells and extending our analysis to other cellular models, we found that mitochondrial localization of the receptor is a widespread characteristic of proliferating cells, and the association of the VDR with proliferation was reinforced by the results of our analysis of differentiated cells. We observed decreased mitochondrial VDR levels in two different models of differentiated cells. In our opinion, this is an interesting observation that warrants further investigation of the metabolic impact and molecular mechanisms governing VDR downregulation in quiescent cells. Previous literature described the differentiating properties of vitamin D, traditionally mediated by nuclear effects of VDR on transcription. However cancer cells are often resistant to the antiproliferative and differentiating properties of vitamin D, as a result of the increased association of the VDR with corepressors on chromatine. This has been reported for skin cancer, among the others. The human proliferating keratinocyte cell line HaCaT does not respond to the antiproliferative action of vitamin D, and we previously demonstrated that nuclear translocation of the VDR, which is a prerequisite for transcriptional activity, is not induced upon ligand stimulation, thus indicating ineffective, or feeble, nuclear VDR signaling in these cells. Therefore, HaCaT cells represent a good model that can be used to examine the mitochondrial effects of VDR activity in a background were the differentiating properties of vitamin D have been lost.