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Characterization of OPA1 isoforms isolated from mouse tissues

Item Type:Article
Title:Characterization of OPA1 isoforms isolated from mouse tissues
Creators Name:Akepati, V.R. and Mueller, E.C. and Otto, A. and Strauss, H. and Portwich, M. and Alexander, C.
Abstract:OPA1, a nuclear encoded mitochondrial protein causing autosomal dominant optic atrophy, is a key player in mitochondrial fusion and cristae morphology regulation. In the present study we have compared the OPA1 transcription and translation products of different mouse tissues. Unlike in humans, we found only two exons (4b and 5b) to be involved in alternative splicing. The relative abundance of the resulting four different splice variants is tissue dependent. Proteolytic cleavage by mitochondrial processing peptidase generates two long forms, isoforms 1 and 7, which lead to three short forms representing the end products after further proteolytic processing. In contrast, isoforms 5 and 8 are directly processed into their coresponding short forms. Short form 1 molecules form 184 kDa dimers, whereas all other isoforms contribute to 285 kDa complexes. Coiled-coil domains of the OPA1 protein specifically homo associate and may be involved in the formation of these complexes. Furthermore, the region encoded by exon 5b inhibits the self-association of coiled-coil domain-I. Finally, our data pinpoint isoform 1 as the, by far, most abundant isoform in the nervous tissue. We postulate that manipulation of isoform 1 protein levels in relation to the other isoforms induces changes of the mitochondrial network in the cell and therefore, mutations affecting the level of functional isoform 1 could lead to devastating effects on retinal ganglion cells.
Keywords:Mitochondria, OPA1, Splice Forms, Protein Isoforms, Coiled-Coil, Animals, Mice
Source:Journal of Neurochemistry
Page Range:372-383
Date:July 2008
Official Publication:https://doi.org/10.1111/j.1471-4159.2008.05401.x
PubMed:View item in PubMed

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