Purinergic signalling mobilizes mitochondrial Ca²⁺ in mouse Sertoli cells

Abstract

Non-technical summary In mammalian testes, Sertoli cells play a key physiological role in germ cell development. Previous research has implicated local ATP release as a potential mechanism of Sertoli cell stimulation. We show that, in mouse Sertoli cells, two different receptor proteins are activated by ATP. Receptor activation, in turn, causes elevation of calcium ion levels inside the cells. By using a novel method to visualize such calcium signals, we identify mitochondria as essential elements of calcium regulation in the testis.Abstract Intimate bidirectional communication between Sertoli cells and developing germ cells ensures the integrity and efficiency of spermatogenesis. Yet, a conceptual mechanistic understanding of the physiological principles that underlie Sertoli cell autocrine and paracrine signalling is lacking. Here, we characterize a purinergic Ca 2+ signalling network in immature mouse Sertoli cells that consists of both P2X2 and P2Y2 purinoceptor subtypes, the endoplasmic reticulum and, notably, mitochondria. By combining a transgenic mouse model with a dedicated bioluminescence imaging device, we describe a novel method to monitor mitochondrial Ca 2+ mobilization in Sertoli cells at subcellular spatial and millisecond temporal resolution. Our data identify mitochondria as essential components of the Sertoli cell signalling 'toolkit' that control the shape of purinergic Ca 2+ responses, and probably several other paracrine Ca 2+ -dependent signals.

Purinergic signalling in the reproductive system in health and disease

“…mRNA for P2Y 1 , P2Y 2 and P2X4 and P2X7 receptors was expressed in cultured rat Sertoli cells [214]. It has been claimed that mitochondria are essential components of Sertoli cell signalling that control purinergic Ca 2+ responses, mediated by P2X2 and P2Y 2 receptors [414].…”

Mitochondrial calcium uptake

“…In 1992, a very influential study (3) showed that mitochondrial Ca 2+ uptake was a genuine cellular mechanism. Recently, investigations in diverse tissues, including cardiac and skeletal muscle, liver cells, and neurons, have raised the possibility that mitochondria also serve as large and dynamic physiological buffers for Ca 2+ (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). However, this point has been debated (16), and forces the question: How much Ca 2+ moves into and out of the mitochondria under normal conditions?…”

Purinergic signaling pathways in endocrine system

“…The P2X2R, P2X3R, and P2X5R subtypes have been identified in various germ cell types, whereas Sertoli cells express P2X2R, P2X3R, and P2X7R (Glass et al, 2001a) as well as the calcium-mobilizing P2Y 2 R (Rudge et al, 1995). Calcium signals generated by activated P2XRs and P2YRs in mouse Sertoli cells are coupled to mobilization of mitochondrial calcium (Veitinger et al, 2011). In addition to P2XRs and P2YRs, A 1 Rs have been found in the crude particulate preparation from rat testis and Sertoli cell enriched cultures (Conti et al, 1988; Monaco et al, 1986; Stiles et al, 1986).…”