Skip to main content
Fig. 1 | Intensive Care Medicine Experimental

Fig. 1

From: Succinate and the shortcut to the cure of metformin-induced lactic acidosis

Fig. 1

Succinate ameliorates mitochondrial oxygen use and energy production when complex I is inhibited, as during metformin intoxication

Respiratory electron transfer and phosphorylation of ADP to produce ATP are indirectly coupled through the proton-motive force that is generated by the activity of the electron transport chain [8]. At toxic dose, metformin somehow inhibits complex I; the flow of electrons through the respiratory chain and related mitochondrial oxygen use, proton-motive force, and energy production accordingly decrease. Succinate delivered into the cell is oxidized to fumarate (as part of the Krebs cycle) by the succinate dehydrogenase, a subunit of the respiratory chain complex II. This reaction is coupled with the direct transfer of electrons to ubiquinone (Q) and to the more distal part of the respiratory chain, independent of complex I. Thanks to this “bypass” strategy, succinate improves mitochondrial respiration, coupled proton extrusion, and energy production during metformin intoxication.

Back to article page