|ZFIN ID: ZDB-PUB-170517-8|
Ca2+ binding to F-ATP synthase β subunit triggers the mitochondrial permeability transition.
Giorgio, V., Burchell, V., Schiavone, M., Bassot, C., Minervini, G., Petronilli, V., Argenton, F., Forte, M., Tosatto, S., Lippe, G., Bernardi, P.
|Source:||EMBO reports 18(7): 1065-1076 (Journal)|
|Registered Authors:||Argenton, Francesco, Schiavone, Marco|
|Keywords:||ATP synthase, calcium, channels, mitochondria, permeability transition|
|PubMed:||28507163 Full text @ EMBO Rep.|
Giorgio, V., Burchell, V., Schiavone, M., Bassot, C., Minervini, G., Petronilli, V., Argenton, F., Forte, M., Tosatto, S., Lippe, G., Bernardi, P. (2017) Ca2+ binding to F-ATP synthase β subunit triggers the mitochondrial permeability transition.. EMBO reports. 18(7):1065-1076.
ABSTRACTF-ATP synthases convert the electrochemical energy of the H+ gradient into the chemical energy of ATP with remarkable efficiency. Mitochondrial F-ATP synthases can also undergo a Ca2+-dependent transformation to form channels with properties matching those of the permeability transition pore (PTP), a key player in cell death. The Ca2+ binding site and the mechanism(s) through which Ca2+ can transform the energy-conserving enzyme into a dissipative structure promoting cell death remain unknown. Through in vitro, in vivo and in silico studies we (i) pinpoint the "Ca2+-trigger site" of the PTP to the catalytic site of the F-ATP synthase β subunit and (ii) define a conformational change that propagates from the catalytic site through OSCP and the lateral stalk to the inner membrane. T163S mutants of the β subunit, which show a selective decrease in Ca2+-ATP hydrolysis, confer resistance to Ca2+-induced, PTP-dependent death in cells and developing zebrafish embryos. These findings are a major advance in the molecular definition of the transition of F-ATP synthase to a channel and of its role in cell death.
- Antibodies (1)