Novel variants of human SCaMC-3, an isoform of the ATP-Mg/P(i) mitochondrial carrier, generated by alternative splicing from 3'-flanking transposable elements.
CaMCs (calcium-dependent mitochondrial carriers) represent a novel subfamily of metabolite carriers of mitochondria. The ATP-Mg/P(i) co-transporter, functionally characterized more than 20 years ago, has been identified to be a CaMC member. There are three isoforms of the ATP-Mg/P(i) carrier in mammals, SCaMC-1 (short CaMC-1), -2 and -3 (or APC-1, -3 and -2 respectively), corresponding to the genes SLC25A24, SLC25A25 and SLC25A23 respectively, as well as six N-terminal variants generated by alternative splicing for SCaMC-1 and -2 isoforms. In the present study, we describe four new variants of human SCaMC-3 generated by alternative splicing. The new mRNAs use the exon 9 3'-donor site and distinct 5'-acceptor sites from repetitive elements, in regions downstream of exon 10, the last exon in all SCaMCs. Transcripts lacking exon 10 (SCaMC-3b, -3b', -3c and -3d) code for shortened proteins lacking the last transmembrane domain of 422, 456 and 435 amino acids, and were found in human tissues and HEK-293T cells. Mitochondrial targeting of overexpressed SCaMC-3 variants is incomplete. Surprisingly, the import impairment is overcome by removing the N-terminal extension of these proteins, suggesting that the hydrophilic N-terminal domain also participates in the mitochondrial import process, as shown for the CaMC members aralar and citrin [Roesch, Hynds, Varga, Tranebjaerg and Koehler (2004) Hum. Mol. Genet. 13, 2101-2111].
Del Arco
Araceli
A
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa UAM-CSIC, Facultad de Ciencias, Universidad Autónoma, 28049 Madrid, Spain. adelarco@cbm.uam.es
D024509:3' Flanking Region / Q000502:physiology*; D017398:Alternative Splicing; D000818:Animals; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D004251:DNA Transposable Elements; D006801:Humans; D008928:Mitochondria; D024101:Mitochondrial Proteins / Q000737:chemistry* / Q000235:genetics*; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
C086357:ATP-Mg-Pi carrier proteins, mitochondria; D017920:Antiporters; D004251:DNA Transposable Elements; D024101:Mitochondrial Proteins; D020033:Protein Isoforms