Sodium butyrate opens mitochondrial permeability transition pore (MPTP) to induce a proton leak in induction of cell apoptosis

• Published in: Biochemical and biophysical research communications 2020-06, Vol.527 (3), p.611-617
• Main Authors: Qin, Xiaojiao, Xu, Yanhong, Peng, Shiqiao, Qian, Shengnan, Zhang, Xiaoying, Shen, Shuang, Yang, Jiajun, Ye, Jianping
• Format: Article
• Language: English
• Subjects: ANT; Apoptosis; Apoptosis - drug effects; ATP; Butyric Acid - pharmacology; Cell Line, Tumor; Glioma; Glioma - drug therapy; Glioma - metabolism; Humans; Membrane Potential, Mitochondrial - drug effects; Mitochondrial Permeability Transition Pore - metabolism; MPTP; Protons
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.04.133

Induction of apoptosis is a strategy in the treatment of glioma, a malignant tumor with the highest prevalence in the brain. Sodium butyrate (NaB) induces apoptosis in glioma cells at pharmacological dosages (>2.5 mM), but the mechanism remains largely unknown beyond the mitochondrial potential drop. In this study, NaB was found to open the mitochondrial permeability transient pore (MPTP) to induce a proton leak in the mechanism of apoptosis. The MPTP opening led to collapse of mitochondrial potential and suppression of ATP production in the NaB-treated cells. Proton leak was increased in the mitochondria under the coupling and uncoupling conditions from the MPTP opening. The proton leak was associated with an elevation in the protein abundance of adenine nucleotide translocator 2 (ANT2) and was blocked by an ANT-specific inhibitor of bongkrekic acid (BA). These data suggest that the proton leak is induced by NaB for the mitochondrial potential drop in the induction of apoptosis. The mechanism may be related to activation of ANT2 in the MPTP complex. •Butyrate induced opening of the mitochondrial permeability transition pore (MPTP).•Butyrate increased proton leak under coupling and uncoupling conditions.•The butyrate activities were associated with mitochondrial potential drop for apoptosis in tumor cells.•The butyrate activities were observed with ANT2 protein elevation and were blocked by the ANT inhibitor.