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Publication : Identification and evolutionary analysis of tissue-specific isoforms of mitochondrial complex I subunit NDUFV3.

First Author  Guerrero-Castillo S Year  2017
Journal  Biochim Biophys Acta Volume  1858
Issue  3 Pages  208-217
PubMed ID  27988283 Mgi Jnum  J:250930
Mgi Id  MGI:6104883 Doi  10.1016/j.bbabio.2016.12.004
Citation  Guerrero-Castillo S, et al. (2017) Identification and evolutionary analysis of tissue-specific isoforms of mitochondrial complex I subunit NDUFV3. Biochim Biophys Acta 1858(3):208-217
abstractText  Mitochondrial complex I is the largest respiratory chain complex. Despite the enormous progress made studying its structure and function in recent years, potential regulatory roles of its accessory subunits remained largely unresolved. Complex I gene NDUFV3, which occurs in metazoa, contains an extra exon that is only present in vertebrates and thereby evolutionary even younger than the rest of the gene. Alternative splicing of this extra exon gives rise to a short NDUFV3-S and a long NDUFV3-L protein isoform. Complexome profiling revealed that the two NDUFV3 isoforms are constituents of the multi-subunit complex I. Further mass spectrometric analyses of complex I from different murine and bovine tissues showed a tissue-specific expression pattern of NDUFV3-S and NDUFV3-L. Hence, NDUFV3-S was identified as the only isoform in heart and skeletal muscle, whereas in liver, brain, and lung NDUFV3-L was expressed as the dominant isoform, together with NDUFV3-S present in all tissues analyzed. Thus, we identified NDUFV3 as the first out of 30 accessory subunits of complex I present in vertebrate- and tissue-specific isoforms. Interestingly, the tissue-specific expression pattern of NDUFV3-S and NDUFV3-L isoforms was paralleled by changes in kinetic parameters, especially the substrate affinity of complex I. This may indicate a regulatory role of the NDUFV3 isoforms in different vertebrate tissues.
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