Work

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

Year: 2024

Type: article

Abstract: 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 F 1 F O -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 F 1 F O -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. • IO-SMPs exhibit a strong protective effect against mPTP opening. • IO-SMPs are unable to modulate the function of enzymatic complexes involved in mPTP formation. • Membrane-bound enzyme complexes' functionality modulated by IO-SMPs might desensitize mPTP opening.

Source: Biochimica et Biophysica Acta (BBA) - Bioenergetics

DOI: 10.1016/j.bbabio.2024.149528