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J. Biol. Chem., Vol. 283, Issue 22, 15300-15308, May 30, 2008

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Peroxisomes as Novel Players in Cell Calcium Homeostasis^*

Francesco Massimo Lasorsa¹, Paolo Pinton¹, Luigi Palmieri, Pasquale Scarcia, Hanspeter Rottensteiner^¶, Rosario Rizzuto², and Ferdinando Palmieri³

From the Department of Pharmaco-Biology, Laboratory of Biochemistry and Molecular Biology, University of Bari and CNR Institute of Biomembranes and Bioenergetics, Via Orabona 4, 70125 Bari, Italy, the Department of Experimental and Diagnostic Medicine, Section of General Pathology, University of Ferrara, 44110 Ferrara, Italy, and the ^¶Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany

Ca²⁺ concentration in peroxisomal matrix ([Ca²⁺]_perox) has been monitored dynamically in mammalian cells expressing variants of Ca²⁺-sensitive aequorin specifically targeted to peroxisomes. Upon stimulation with agonists that induce Ca²⁺ release from intracellular stores, peroxisomes transiently take up Ca²⁺ reaching peak values in the lumen as high as 50–100 µM, depending on cell types. Also in resting cells, peroxisomes sustain a Ca²⁺ gradient, [Ca²⁺]_perox being 20-fold higher than [Ca²⁺] in the cytosol ([Ca²⁺]_cyt). The properties of Ca²⁺ traffic across the peroxisomal membrane are different from those reported for other subcellular organelles. The sensitivity of peroxisomal Ca²⁺ uptake to agents dissipating H⁺ and Na⁺ gradients unravels the existence of a complex bioenergetic framework including V-ATPase, Ca²⁺/H⁺, and Ca²⁺/Na⁺ activities whose components are yet to be identified at a molecular level. The different [Ca²⁺]_perox of resting and stimulated cells suggest that Ca²⁺ could play an important role in the regulation of peroxisomal metabolism.

Received for publication, January 24, 2008 , and in revised form, March 25, 2008.

^* This work was supported by grants from Ministero dell'Università e della Ricerca, Ministero della Salute, Center of Excellence in Genomics, Apulia Region and European Community's Sixth Programme for Research Contract LSHM-CT-2004-503116, Telethon Grant GGP05284, the Italian Association for Cancer Research, local funds from the Universities of Bari and Ferrara, European Union Fondi Strutturali Obiettivo 2, the Regional Program for Industrial Research, Innovation and Technological Transfer of the Emilia Romagna Region, and the Italian Space Agency. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These authors equally contributed to this work.

² To whom correspondence may be addressed. Tel.: 39-532291361; Fax: 39-532247278; E-mail: r.rizzuto{at}unife.it. ³ To whom correspondence may be addressed. Tel.: 39-805443374; Fax: 39-805442770; E-mail: fpalm{at}farmbiol.uniba.it.

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