Inside-out submitochondrial particles affect the mitochondrial permeability transition pore opening under conditions of mitochondrial dysfunction

The inside-out submitochondrial particles (IO-SMPs) showed a strong protective effect against mitochondrial permeability transition pore (mPTP) opening in mitochondria isolated from swine hearts 3 h after explantation. The latter condition was used to emulate situation of mitochondrial damage. We identified that the protective effect of IO-SMPs cannot be attributed to a functional modulation of the enzymatic complexes involved in mPTP formation. Indeed, oxidative phosphorylation and F1FO-ATPase activity were not affected. Conversely, mPTP desensitization might be caused by structural modification. IO-SMP incorporation into the mitochondria can modulate the membrane-bound enzyme complexes' functionality, inducing F1FO-ATPase to be unable to carry out the conformational changes useful for mPTP opening. Thus, the data are a valid starting point for IO-SMP application in the treatment of impaired cardiovascular conditions supported by mPTP opening.