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, 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 the lumen of the c-subunit ring of the ATP synthase, upon dissociation from the catalytic domain. 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 evaluate the likelihood that this lumen is hydrated rather than empty or blocked by lipid molecules. These calculations demonstrate that the properties of the lumen of a correctly assembled c-ring are inconsistent with those attributed to the MPTP.
- Wenchang Zhou
- José D Faraldo-Gómez
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Yibing Shan, DE Shaw Research, United States
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