title: Mitochondria and AMP-activated protein kinase-dependent mechanism of efferocytosis.
abstract: Defective clearance of apoptotic cells is frequently associated with perpetuation of inflammatory conditions. Our results show a rapid activation of AMP-activated kinase (AMPK) in macrophages upon exposure to apoptotic cells or lysophosphatidylcholine, a specific phospholipid that is produced and released from dying cells. AMPK activation resulted from inhibition of mitochondrial oxygen consumption and ATP production and further depended on Ca(2+) mobilization and mitochondrial reactive oxygen species generation. Once activated, AMPK increased microtubule synthesis and chemokinesis and provided adaptation to energy demand during tracking and engulfment. Uptake of apoptotic cells was increased in lungs of mice that received lysophosphatidylcholine. Furthermore, inhibition of AMPK diminished clearance of apoptotic thymocytes in vitro and in dexamethasone-treated mice. Taken together, we conclude that the mitochondrial AMPK axis is a sensor and enhancer of tracking and removal of apoptotic cell, processes crucial to resolution of inflammatory conditions and a return to tissue homeostasis.
authors.affiliation: From the Department of Medicine.
authors.forename: Shaoning
authors.initials: S
authors.lastname: Jiang
authors.affiliation: From the Department of Medicine,; the Division of Infectious Diseases, Korea University Ansan Hospital, Ansan 425-707, Republic of Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Park
authors.affiliation: From the Department of Medicine.
authors.forename: William S
authors.initials: WS
authors.lastname: Stigler
authors.affiliation: Department of Anesthesiology.
authors.forename: Judy
authors.initials: J
authors.lastname: Creighton
authors.affiliation: Department of Pathology, and.
authors.forename: Saranya
authors.initials: S
authors.lastname: Ravi
authors.affiliation: Department of Pathology, and; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012 and.
authors.forename: Victor
authors.initials: V
authors.lastname: Darley-Usmar
authors.affiliation: From the Department of Medicine,; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0012 and. Electronic address: zmijewsk@uab.edu.
authors.forename: Jaroslaw W
authors.initials: JW
authors.lastname: Zmijewski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D008244:Lysophosphatidylcholines; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated Kinase (AMPK); Bioenergetics; Chemotaxis; Mitochondria; Phagocytosis
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