2-Methylcitric acid (Methylcitric acid) is an endogenous metabolite within the 2-methylcitric acid cycle, known to accumulate in conditions such as methylmalonic and propionic acidemias.

2-Methylcitric acid compromises glutamate metabolism and triggers permeability transition in brain mitochondria by inhibiting glutamate dehydrogenase (GDH) at concentrations as low as 0.5 mM. At levels between 1-3 mM over 150 seconds, it significantly reduces mitochondrial membrane potential and causes swelling in Ca2+-laden mitochondria with various substrates. It acts as a potent block to glutamate oxidation through GDH activity inhibition and induces permeability transition, thus disrupting mitochondrial energy balance. However, 2-Methylcitric acid does not markedly affect mitochondrial glutamate transport, including in liver mitochondria.