Rare diseases affect over 300 million people worldwide and are often caused by genetic variants. While variant detection has become cost-effective, interpreting these variants-particularly collecting Show more
Rare diseases affect over 300 million people worldwide and are often caused by genetic variants. While variant detection has become cost-effective, interpreting these variants-particularly collecting literature-based evidence like ACMG/AMP PM3-remains complex and time-consuming. Show less
Todd P. Silverstein · 2024 · The Journal of Physical Chemistry B · ACS Publications · added 2026-04-20
In a recent series of papers, James W. Lee reported that mitochondrial oxidative phosphorylation violates the second law of thermodynamics and that it is allowed to do so because it is a "Type-B" proc Show more
In a recent series of papers, James W. Lee reported that mitochondrial oxidative phosphorylation violates the second law of thermodynamics and that it is allowed to do so because it is a "Type-B" process that features lateral and longitudinal membrane asymmetry. We show here that these contentions are based on problematic interpretations of the literature. More reliable values of ΔGredox and ΔGATP synthesis show that the second law is not violated. More recent reports on the structures of the redox-driven proton pumps (Complexes I, III, and IV) suggest that longitudinal membrane asymmetry does not exist. Finally, Lee's predictions for the concentration of protons localized at the P-side surface of the bioenergetic membrane are likely to be much too high due to several errors; thus, his predicted high values of ΔpHsurface that violate the second law are likely to be wrong. There is currently no strong experimental or theoretical evidence to support the contention that oxidative phosphorylation violates the second law of thermodynamics. Show less