Growth hormone activity in mitochondria depends on GH receptor Box 1 and involves caveolar pathway targeting

Journal Article · Wed Feb 01 04:00:00 EST 2006 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.10.027· OSTI ID:20775332

Perret-Vivancos, Cecile ^[1]; Abbate, Aude ^[1]; Ardail, Dominique ^[2]; Raccurt, Mireille ^[1]; Usson, Yves ^[3]; Lobie, Peter E ^[4]; Morel, Gerard ^[1]

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1. CNRS UMR 5123, Bat. R. Dubois, Universite Claude Bernard-Lyon 1, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex (France)
2. INSERM U189-Faculte de medecine Lyon Sud, 69921 Oullins cedex (France)
3. UMR 5525 CNRS, Institut de l'Ingenierie de l'Information de Sante (IN3S) Domaine de la Merci, Universite Joseph Fourier, 38706 La Tronche cedex (France)
4. Liggins Institute, University of Aukland, 2-6 Park Avenue, Private Bag, Aukland 92019 (New Zealand)

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.

• OSTI ID: 20775332
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 3 Vol. 312; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENINES
BIOLOGICAL EFFECTS
CHO CELLS
FLUORESCENCE
HAMSTERS
MITOCHONDRIA
MUTATIONS
NICOTINE
OVARIES
POLAROGRAPHY
RATS
RECEPTORS
SPECTROSCOPY
STH