Mitochondrial Permeation Transition Pore (MPTP)
I believe there is evidence that using the mitochondrial protocol consisting of methylb12, meta-folate, trimethylglycine is akin to trying to patch up a hole in the hull of the ship. Water is gushing in fast and wreaking havoc on board, we are using supplements simply as treatments to correct mitochondrial deficits internally , yet what we need to control is the perimeter of the mitochondria, also known as the MPTP (Mitochondrial Permeation Transition Pore). This controls the flow of molecules in and out of this structure.
One way to help make the mitochondria less permeable to many extracellular components such as excessive calcium influx (in many cases induced by glutamate transmission) is to reduce the permeability of the pore. Research shows the drugs such as the powerful immunosuppressant Cyclosporin A has a side effect of doing this. Also a drug with a high safety record is Trimetazidine, currently used to treat angina. It has been shown to increase levels of ATP and also reduce production of free radicals. I believe some synergy would occur using Trimetazidine in conjunction with a glutamate modulator. Or alternatively using Trimetazidine alongside the mitochondrial protocol could possibly enhance the efficacy of this treatment strategy.
I will provide references shortly when I get the time.