AMP-activated protein kinase (AMPK) and Mitochondrial respiratory chain complex I (AMPK (for AMP-activated protein kinase), Complex I (for mitochondrial respiratory chain complex I))

AMP-activated protein kinase (AMPK) is a master metabolic sensor activated by increases in AMP/ATP and ADP/ATP ratios during energy stress; it is a serine/threonine kinase composed of α, β, and γ subunits and regulates key metabolic pathways to restore cellular energy homeostasis. Mitochondrial respiratory chain complex I is the first enzyme of the mitochondrial electron transport chain, catalyzing the transfer of electrons from NADH to ubiquinone and playing a critical role in ATP synthesis by generating the proton gradient necessary for oxidative phosphorylation. Pharmacological inhibition of Complex I increases the AMP/ATP ratio, activating AMPK, which shifts cellular metabolism toward catabolic processes, promotes mitochondrial biogenesis, and is cytoprotective. Dysfunction in either pathway is implicated in metabolic, neurodegenerative, and cardiovascular diseases, and both are well-established drug targets for conditions like diabetes (metformin), obesity, and cancer.

Other names

AMP-activated protein kinase5' AMP-activated protein kinasePRKAANADH:ubiquinone oxidoreductaseNADH dehydrogenase

Inhibition of mitochondrial Complex I increases AMP/ATP ratio, indirectly activating AMPK. Direct activation of AMPK promotes catabolic pathways, suppresses anabolic processes, increases mitochondrial biogenesis, and promotes cell survival under stress. Drug-induced inhibition of Complex I leads to metabolic stress and AMPK activation, used in treatment of type 2 diabetes (metformin) and for cytoprotection in ischemia.