SCaMC-1Like a Member of the Mitochondrial Carrier (MC) Family Preferentially Expressed in Testis and Localized in Mitochondria and Chromatoid Body

Abstract

Mitochondrial carriers (MC) form a highly conserved family involved in solute transport across the inner mitochondrial membrane in eukaryotes. In mammals, ATP-Mg/Pi carriers, SCaMCs, form the most complex subgroup with four paralogs, SCaMC-1, -2, -3 and -3L, and several splicing variants. Here, we report the tissue distribution and subcellular localization of a mammalian-specific SCaMC paralog, 4930443G12Rik/SCaMC-1Like (SCaMC-1L), which displays unanticipated new features. SCaMC-1L proteins show higher amino acid substitution rates than its closest paralog SCaMC-1. In mouse, SCaMC-1L expression is restricted to male germ cells and regulated during spermatogenesis but unexpectedly its localization is not limited to mitochondrial structures. In mature spermatids SCaMC-1L is detected in the mitochondrial sheath but in previous differentiation stages appears associated to cytosolic granules which colocalize with specific markers of the chromatoid body (CB) in post-meiotic round spermatids and inter-mitochondrial cement (IMC) in spermatocytes. The origin of this atypical distribution was further investigated by transient expression in cell lines. Similarly to male germ cells, in addition to mitochondrial and cytosolic distribution, a fraction of SCaMC-1L-expressing COS-7 cells display cytosolic SCaMC-1L-aggregates which exhibit aggresomal-like features as the CB. Our results indicate that different regions of SCaMC-1L hinder its import into mitochondria and this apparently favours the formation of cytosolic aggregates in COS-7 cells. This mechanism could be also operational in male germ cells and explain the incorporation of SCaMC-1L into germinal granules.

Argonaute2 Protein in Rat Spermatogenic Cells Is Localized to Nuage Structures and LAMP2-Positive Vesicles Surrounding Chromatoid Bodies

“…Our 2005 study also showed that proteins associated with the nucleus, cytosol, and mitochondria are present in CBs (Haraguchi et al 2005). In a mouse study, Amigo et al (2012) reported that SCaMC-1L, a subgroup of ATP-Mg/Pi carriers, is expressed exclusively in male germ cells, is regulated during spermatogenesis, and is found in CBs in round spermatids and IMC in spermatocytes, as well as in mitochondria. In transient expression experiments, SCaMC-1L in COS-7 cells formed aggregates that displayed aggresome-like features similar to those of CBs.…”

A Self-Sequestered Calmodulin-like Ca2+ Sensor of Mitochondrial SCaMC Carrier and Its Implication to Ca2+-Dependent ATP-Mg/Pi Transport

“…While AAC accounts for the bulk ADP/ATP recycling in the matrix by exporting newly synthesized ATP out of the matrix while importing ADP for continuous synthesis (Traba et al, 2009b), the transport activity of SCaMC is important for mitochondrial activities that depend on adenine nucleotides, such as gluconeogenesis, mitochondrial biogenesis and mitochondrial DNA maintenance (Amigo et al, 2013; Cavero et al, 2005; Chen et al, 2011; Kucejova et al, 2008; Llorente-Folch et al, 2013; Satrustegui et al, 2007). SCaMC is abundant, and to date, five major paralogs have been identified, SCaMC-1/SLC25A24, SCaMC-2/SLC25A25, SCaMC-3/SLC25A23 (Bassi et al, 2005; del Arco and Satrustegui, 2004; Fiermonte et al, 2004; Mashima et al, 2003), SCaMC-1L (Amigo et al, 2012) and SCaMC-3L (Traba et al, 2009a), most of which have several alternative spliced variants (del Arco and Satrustegui, 2004). The major difference between SCaMC and AAC is the specific regulation of only SCaMC by Ca 2+ .…”

Glucagon Regulation of Oxidative Phosphorylation Requires an Increase in Matrix Adenine Nucleotide Content through Ca2+ Activation of the Mitochondrial ATP-Mg/Pi Carrier SCaMC-3

“…11). To date, five different paralogs, termed SCaMC (short calcium-binding mitochondrial carrier) 1-3, -1-like and -3-like, have been described in mammals (9,10,(12)(13)(14), of which two, SCaMC-1-like and SCaMC-3-like, are only expressed in testis. In addition, several splicing isoforms have been described (9), making it the most complex subgroup of mitochondrial carriers (15).…”