Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 129, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2020.105879
Keywords
Nicotinic acetylcholine receptor; Mitochondria; Bax; Voltage-dependent anion channel; Apoptosis
Categories
Ask authors/readers for more resources
Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in muscles and autonomic ganglia and regulate cytokine and neurotransmitter release in the brain and non-excitable cells. The alpha 7 nAChRs localized in the outer membrane of mitochondria regulate cytochrome c release stimulated by apoptosis-inducing agents. However, the mechanisms through which nAChRs influence mitochondrial permeability remain obscure. Here we put an aim to explore the interaction of nAChRs with voltage-dependent anion channels (VDAC1) and proapoptotic protein Bax in the course of apoptosis induction. By using molecular modeling in silico, it was shown that both Bax and VDAC1 can bind within the 4th transmembrane portion (M4) of nAChR subunits. Experimentally, alpha 7 nAChR-Bax and alpha 7 nAChR-VDAC1 complexes were identified by sandwich ELISA in mitochondria isolated from astrocytoma U373 cells. Stimulating apoptosis of U373 cells by H2O2 disrupted alpha 7-VDAC complexes and favored formation of alpha 7-Bax complexes accompanied by cytochrome c release from mitochondria. alpha 7-selective agonist PNU282987 or type 2 positive allosteric modulator PNU120596 disrupted alpha 7-Bax and returned alpha 7 nAChR to complex with VDAC1 resulting in attenuation of cytochrome c release. It is concluded that mitochondrial nAChRs regulate apoptosis-induced mitochondrial channel formation by modulating the interplay of apoptosis-related proteins in mitochondria outer membrane.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available