Commentary: Why do many cell biology papers contain fundamental bioenergetic errors?

To professional bioenergeticists, the thermodynamic and kinetic constraints on mitochondrial function are self-evident. It is therefore profoundly concerning that high-profile cell biology papers continue to appear containing fundamental bioenergetic errors that appear to have evaded the scrutiny of the principal investigator, co-authors, editors and, apparently, at least some of the referees. The problem is not new, and seems to stem from a perception that bioenergetics is a 'difficult' subject, both at undergraduate level, if it is taught in any depth, and in research, where cell biologists are faced with biophysical concepts such as protonmotive force, ion flux, redox potential and Gibbs free energy.

Brain mitochondrial calcium transport: Origins of the set-point concept and its application to physiology and pathology.

The transport of calcium across the inner mitochondrial membrane plays a key role in neuronal physiology and pathology. The kinetic responses of the uniporter and efflux pathways are such that a cytosolic free calcium 'set-point' can be established - above which there is net calcium accumulation into the matrix that is reversed when plasma membrane transport lowers cytosolic calcium. Pathological activation of N-methyl-d-aspartate receptor mediated sodium and calcium entry into the neuron, as occurs in stroke and spreading depression, places severe demands on both the ATP-generating and calcium loading capacities of the neuronal mitochondria as the set-point is exceeded.