title: Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting.
abstract: Growth hormone (GH) binding to its receptor (GHR) initiates GH-dependent signal transduction and internalization pathways to generate the biological effects. The precise role and way of action of GH on mitochondrial function are not yet fully understood. We show here that GH can stimulate cellular oxygen consumption in CHO cells transfected with cDNA coding for the full-length GHR. By using different GHR cDNA constructs, we succeeded in determining the different parts of the GHR implicated in the mitochondrial response to GH. Polarography and two-photon excitation fluorescence microscopy analysis showed that the Box 1 of the GHR intracellular domain was required for an activation of the mitochondrial respiration in response to a GH exposure. However, confocal laser scanning microscopy demonstrated that cells lacking the GHR Box 1 could efficiently internalize the hormone. We demonstrated that internalization mediated either by clathrin-coated pits or by caveolae was able to regulate GH mitochondrial effect: these two pathways are both essential to obtain the GH stimulatory action on mitochondrial function. Moreover, electron microscopic and biochemical approaches allowed us to identify the caveolar pathway as essential for targeting GH and GHR to mitochondria.
authors.affiliation: CNRS UMR 5123, Bât. R. Dubois, Université Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Perret-Vivancos
authors.forename: Aude
authors.initials: A
authors.lastname: Abbate
authors.forename: Dominique
authors.initials: D
authors.lastname: Ardail
authors.forename: Mireille
authors.initials: M
authors.lastname: Raccurt
authors.forename: Yves
authors.initials: Y
authors.lastname: Usson
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lobie
authors.forename: Gérard
authors.initials: G
authors.lastname: Morel
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000378:metabolism*; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000378:metabolism*; D012119:Respiration; D015398:Signal Transduction; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D011986:Receptors, Somatotropin; D013006:Growth Hormone