Response to Pomozi et al Research Commentary
In the course of studying the effects of ABCC6 deficiency in mice, we observed an enrichment of mitochondrial gene expression signatures. In subsequent studies we found that ABCC6 null mice exhibited abnormal mitochondrial morphology and functional mitochondrial deficiencies.1 We then carried out subcellular fractionation studies indicating that ABCC6 co-localized with markers of the mitochondria-associated membranes (MAM) in mouse liver and kidney.1 Our results differed from Le Saux et al (2011), from the Varadi group who had concluded in a recent publication that ABCC6 resided in the plasma membrane.2 To test whether ABCC6 was localized in plasma membrane, we performed cell surface protein biotin labeling experiments, which were negative for ABCC6.1
Pomozi et al3 of the Varadi group have now challenged our conclusions based, as in their previous report,2 on immunofluorescence imaging of frozen liver sections and cells in culture showing peripheral cellular localization of antibody binding. They argue that cell disruption and subcellular fractionation in our study1 may have resulted in artifactual associations of membrane proteins. However, this seems improbable given that the plasma membrane markers that we examined did not fractionate with ABCC6, and MAM constitutes a very small fraction of the total membranes.1 [Extract]
- Received April 24, 2013.
- Accepted April 25, 2013.