Abstract 12454: Mitochondrial Transcription Factor 2B as a Mediator of Mitochondrial Retrograde Signaling and Endothelial Cell Shape
Mitochondrial dysfunction, such as observed in endothelial cells, has been implicated in various cardiovascular diseases including, hypertension and atherosclerosis. Mitochondrial transcription factor 2B (TFB2M) is an essential component to maintain proper transcriptional and functional control of mitochondrial DNA. As well, elongation of endothelial cells is a characteristic of atheroprotective regions within the vasculature, and the relationship between the mitochondria and EC shape is currently unknown. Additionally, recent interest has been focused on mechanisms by which the mitochondria may signal to the nucleus to affect cell function. The aim of our study is to investigate the hypothesis that TFB2M has a novel role in enhancing endothelial function. Human umbilical vein endothelial cells (HUVECs) were harvested 72 hours after adenoviral transduction with TFB2M (100 moi). HUVECs transduced with TFB2M showed an elongated cell morphology when compared to GFP control. To further investigate the effect of TFB2M on regulating mitochondrial function and cell shape, immunoblotting was carried out for markers involved in mitochondrial function/dynamics and markers indicative of cytoskeleton reorganization. TFB2M transduction resulted in increased expression of mitochondrial biogenesis marker VDAC (2.6 fold increase), mitochondrial fusion protein MFN2 (2.1 fold increase), and phosphorylated myosin phosphatase targeting protein MYPT1 at Thr850 (2.2 fold increase, p < 0.05 for all proteins). Additionally, fluorescence microscopy showed enhanced mitochondrial fluorescence in TFB2M transduced cells using mitotracker red staining (3.5 fold increase, p < 0.001). These data indicate that TFB2M has a previously undiscovered function contributing to altered EC function and shape, potentially through a novel mitochondrial retrograde signaling mechanism. Further research will focus on distinguishing the exact mechanisms culminating in a protective EC phenotype and the beneficial role of endothelial TFB2M-mediated enhanced mitochondrial function in the treatment of EC dysfunction associated with various cardiovascular diseases.
Author Disclosures: S.J. Forrester: None. T. Kawai: None. K.J. Elliot: None. K. Eguchi: None. J. Park: None. V. Rizzo: None. S. Eguchi: None.
- © 2015 by American Heart Association, Inc.