Patyal 2022 Int J Mol Sci

Patyal P, Nguyen B, Zhang X, Azhar G, Ameer FS, Verma A, Crane J, Kc G, Che Y, Wei JY (2022) Rho/SRF inhibitor modulates mitochondrial functions. https://doi.org/10.3390/ijms231911536

» Int J Mol Sci 23:11536. PMID: 36232837 Open Access

Patyal Pankaj, Nguyen Bachkhoa, Zhang Xiaomin, Azhar Gohar, Ameer Fathima S, Verma Ambika, Crane Jasmine, Kc Grishma, Che Yingni, Wei Jeanne Y (2022) Int J Mol Sci

Abstract: CCG-1423 is a Rho A pathway inhibitor that has been reported to inhibit Rho/SRF-mediated transcriptional regulation. Serum response factor and its cofactors, which include ternary complex factors and myocardin-related transcription factors, regulate various cellular functions. In this study, we observed that CCG-1423 modulates the mitochondrial functions. The effect of this small molecule drug was determined by measuring mitochondrial function using an XFe96 Analyzer and an Oxygraph 2k (O2k) high-resolution respirometer. CCG-1423 treatment significantly reduced oxidative phosphorylation in a dose-dependent manner. However, CCG-1423 increased the glycolytic rate. We also observed that histone 4 at lysine-16 underwent hyperacetylation with the treatment of this drug. Immunolabeling with F-actin and MitoTracker revealed the alteration in the actin cytoskeleton and mitochondria. Taken together, our findings highlight a critical role of CCG-1423 in inhibiting the transcription of SRF/p49 and PGC-1α, β, resulting in the downregulation of mitochondrial genes, leading to the repression of mitochondrial oxidative phosphorylation and overall ATP reduction. This study provides a better understanding of the effects of CCG-1423 on mitochondria, which may be useful for the assessment of the potential clinical application of CCG-1423 and its derivatives. • Keywords: CCG-1423, Acetylation, Mitochondrial function, Serum response factor • Bioblast editor: Plangger M

Labels: MiParea: Respiration 

HRR: Oxygraph-2k 

2023-12