complex+1+of+the+mitochondrial+transport



**Figure 1.** Complex 1 of the mitochondrial transport chain.

Inhibition of complex 1 reduces NADH oxidation (highlighted in yellow) which lowers the proton gradient across the inner mitochondrial membrane and the proton driven synthesis of ATP (Pernicova et al. 2014). The ATP:ADP:AMP synthesis is shifted towards increasing AMP synthesis. With increased AMP levels the adenylate cyclase (membrane bound enzyme that catalyzes the conversion of ATP to cAMP) is inhibited. Therefore cAMP levels are reduced by metformin (Pernicova et al. 2014).