Methylglyoxal disrupts the functionality of rat liver mitochondria

Methylglyoxal (MG) is a reactive metabolite derived from different physiological pathways. Its production can be harmful to cells via glycation reactions of lipids, DNA, and proteins. But, the effects of MG on mitochondrial functioning and bioenergetic responses are still elusive. Then, the effects of MG on key parameters of mitochondrial functionality were examined here. Isolated rat liver mitochondria were exposed to 0.1–10 mM of MG to determine its toxicity in the mitochondrial viability, membrane potential (Δψm), swelling and the superoxide (O2•-) production. Besides, mitochondrial oxidative phosphorylation parameters were analyzed by high-resolution respiratory (HRR) assay. In this set of experiments, routine state, PM state (pyruvate/malate), oxidative phosphorylation (OXPHOS), LEAK respiration, electron transport system (ETS) and oxygen residual (ROX) states were evaluated. HRR showed that PM state, OXPHOS CI-Linked, LEAK respiration, ETS CI/CII-Linked and ETS CII-Linked/ROX were significantly inhibited by MG exposure. MG also inhibited the complex II activity, and decreased Δψm and the viability of mitochondria. Taken together, our data indicates that MG is an inductor of mitochondrial dysfunctions and impairs important steps of respiratory chain, effects that can alter bioenergetics responses. •Methylglyoxal (MG) inhibit the oxidative phosphorylation linked to complex I.•MG reduces the mitochondrial viability and suppresses the complex II.•Electron transport chain and mitochondrial membrane potential are reduced by MG.