title: AMPK-associated signaling to bridge the gap between fuel metabolism and hepatocyte viability.
abstract: The adenosine monophosphate-activated protein kinase (AMPK) and p70 ribosomal S6 kinase-1 pathway may serve as a key signaling flow that regulates energy metabolism; thus, this pathway becomes an attractive target for the treatment of liver diseases that result from metabolic derangements. In addition, AMPK emerges as a kinase that controls the redox-state and mitochondrial function, whose activity may be modulated by antioxidants. A close link exists between fuel metabolism and mitochondrial biogenesis. The relationship between fuel metabolism and cell survival strongly implies the existence of a shared signaling network, by which hepatocytes respond to challenges of external stimuli. The AMPK pathway may belong to this network. A series of drugs and therapeutic candidates enable hepatocytes to protect mitochondria from radical stress and increase cell viability, which may be associated with the activation of AMPK, liver kinase B1, and other molecules or components. Consequently, the components downstream of AMPK may contribute to stabilizing mitochondrial membrane potential for hepatocyte survival. In this review, we discuss the role of the AMPK pathway in hepatic energy metabolism and hepatocyte viability. This information may help identify ways to prevent and/or treat hepatic diseases caused by the metabolic syndrome. Moreover, clinical drugs and experimental therapeutic candidates that directly or indirectly modulate the AMPK pathway in distinct manners are discussed here with particular emphasis on their effects on fuel metabolism and mitochondrial function.
authors.forename: Yoon Mee
authors.initials: YM
authors.lastname: Yang
authors.forename: Chang Yeob
authors.initials: CY
authors.lastname: Han
authors.forename: Yoon Jun
authors.initials: YJ
authors.lastname: Kim
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D019610:Cytoprotection; D004734:Energy Metabolism / Q000187:drug effects; D004789:Enzyme Activation; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control; D008930:Mitochondria, Liver / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D055372:AMP-Activated Protein Kinases