ATP Synthase F 1 Subcomplex is the Gate of the C-Subunit Pore of the Mitochondrial Permeability Transition

2020 ◽  
Author(s):  
Nelli Mnatsakanyan ◽  
Han-A Park ◽  
Jing Wu ◽  
Xiang He ◽  
Marc C. Llaguno ◽  
...  
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
C Subunit

scholarly journals Atomistic simulations indicate the c-subunit ring of the F1Fo ATP synthase is not the mitochondrial permeability transition pore

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Wenchang Zhou ◽  
Fabrizio Marinelli ◽  
Corrine Nief ◽  
José D Faraldo-Gómez
Keyword(s):  
Atp Synthase ◽  
Mitochondrial Permeability Transition Pore ◽  
Catalytic Domain ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Inner Mitochondrial Membrane ◽  
Ion Conductance ◽  
Mitochondrial Permeability ◽  
C Subunit

Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, proposedly due to the opening of a non-selective protein channel of unknown molecular identity. A recent study purports that this channel, referred to as Mitochondrial Permeability Transition Pore (MPTP), is formed within the c-subunit ring of the ATP synthase, upon its dissociation from the catalytic domain of the enzyme. Here, we examine this claim for two c-rings of different lumen width, through calculations of their ion conductance and selectivity based on all-atom molecular dynamics simulations. We also quantify the likelihood that the lumen of these c-rings is in a hydrated, potentially conducting state rather than empty or blocked by lipid molecules. These calculations demonstrate that the structure and biophysical properties of a correctly assembled c-ring are inconsistent with those attributed to the MPTP.

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