Peroxisomal Localization of the Proopiomelanocortin-Derived Peptides β-Lipotropin and β-Endorphin

Author:

Höftberger Romana1,Kunze Markus2,Voigtländer Till1,Unterberger Ursula1,Regelsberger Günther1,Bauer Jan2,Aboul-Enein Fahmy3,Garzuly Ferenc4,Forss-Petter Sonja2,Bernheimer Hanno1,Berger Johannes2,Budka Herbert1

Affiliation:

1. Institute of Neurology (R.H., T.V., U.U., G.R., H.Be., H.Bu.), Division of Neuroimmunology, Medical University of Vienna, A-1097 Vienna, Austria

2. Center for Brain Research (M.K., J.Ba., S.F.-P., J.Be.), Division of Neuroimmunology, Medical University of Vienna, A-1097 Vienna, Austria

3. Department of Neurology (F.A.-E.), SMZ-Ost Danube Hospital, A-1220 Vienna, Austria

4. Department of Pathology (F.G.), Markusovszky Hospital, H-9701 Szombathely, Hungary

Abstract

The peptide hormones ACTH, MSHs, β-lipotropin (β-LPH), and β-endorphin are all derived from the precursor molecule proopiomelanocortin (POMC). Using confocal laser microscopy and immunoelectron microscopy in human pituitary gland, we demonstrate a peroxisomal localization of β-endorphin and β-LPH in cells expressing the peroxisomal ATP-binding cassette-transporter adrenoleukodystrophy protein (ALDP). The peroxisomal localization of β-LPH and β-endorphin was not restricted to the pituitary gland but was additionally found in other human tissues that express high levels of ALDP, such as dorsal root ganglia, adrenal cortex, distal tubules of kidney, and skin. In contrast to the peptide hormones β-LPH and β-endorphin, which are derived from the C terminus of POMC, the N-terminal peptides ACTH, α-MSH, and γ-MSH were never detected in peroxisomes. This novel peroxisomal localization of β-endorphin and β-LPH in ALDP-positive cells was confirmed by costaining with ALDP and the peroxisomal marker catalase. Moreover, peroxisomal sorting of β-LPH could be modeled in HeLa cells by ectopic expression of a POMC variant, modified to allow cleavage and release of β-LPH within the secretory pathway. Although β-LPH and β-endorphin were only associated with peroxisomes in cells that normally express ALDP, the transporter activity of ALDP is not necessary for the peroxisomal localization, as demonstrated in tissues of X-linked adrenoleukodystrophy patients lacking functional ALDP. It remains to be elucidated whether and how the peroxisomal localization of POMC-derived hormones has a role in the endocrine dysfunction of peroxisomal disease.

Publisher

The Endocrine Society

Subject

Endocrinology

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