%0 Journal Article
%T A C-Terminal Transmembrane Anchor Targets the Nuage-Localized Spermatogenic Protein Gasz to the Mitochondrial Surface
%A Yelena Altshuller
%A Qun Gao
%A Michael A. Frohman
%J ISRN Cell Biology
%D 2013
%R 10.1155/2013/707930
%X Mitochondria, normally tubular and distributed throughout the cell, are instead found in spermatocytes in perinuclear clusters in close association with nuage, an amorphous organelle composed of RNA and RNA-processing proteins that generate piRNAs. piRNAs are a form of RNAi required for transposon suppression and ultimately fertility. MitoPLD, another protein required for piRNA production, is anchored to the mitochondrial surface, suggesting that the nuage, also known as intermitochondrial cement, needs to be juxtaposed there to bring MitoPLD into proximity with the remainder of the piRNA-generating machinery. However, the mechanism underlying the juxtaposition is unknown. Gasz, a multidomain protein of known function found in the nuage in vertebrates, is required for piRNA production and interacts with other nuage proteins involved in this pathway. Unexpectedly, we observed that Gasz, in nonspermatogenic mammalian cells lines, localizes to mitochondria and does so through a previously unrecognized conserved C-terminal mitochondrial targeting sequence. Moreover, in this setting, Gasz is able to recruit some of the normally nuage-localized proteins to the mitochondrial surface. Taken together, these findings suggest that Gasz is a nuage-localized protein in spermatocytes that facilitates anchoring of the nuage to the mitochondrial surface where piRNA generation takes place as a collaboration between nuage and mitochondrial-surface proteins. 1. Introduction piRNAs, a third form of RNAi, were initially uncovered as an endogenous mechanism to suppress transposon mobilization during germ cell differentiation (reviewed in [1]). Subsequent studies revealed additional roles in mammalian spermatogenesis for regulation of nontransposon genes [2]. Most of the proteins involved in piRNA generation, which include Argonaut family proteins, piRNA methylases, and Tudor-containing proteins, are found in an RNA-processing organelle known as the nuage, a specialized form of pi-body [3¨C6]. The nuage, also known as ¡°inter-mitochondrial cement,¡± has long been known to be in close association with mitochondria, but the reason for the juxtaposition and the mechanism underlying it has remained unknown. The recent finding that MitoPLD/Zucchini/PLD6, a phospholipase D-family member that localizes to the mitochondrial surface via an N-terminal targeting sequence [7], is required for piRNA generation [8, 9], suggested one reason why the nuage and mitochondria need to be in proximity, but not a mechanism for it, since MitoPLD/Zucchini has not been recovered as part of the
%U http://www.hindawi.com/journals/isrn.cell.biology/2013/707930/