Application Note: Functional Validation Of Genomic And Proteomic Data

Comparative genomic and proteomic analyses have identified approximately half of the estimated 1500 mitochondrial proteins encoded by the human nuclear genome. In recently published studies, XF assays have extended these estimates via the identification of functional roles of some of the nuclear and mtDNA-encoded proteins, and in one case, clarifying assumptions about their activity that had been based on sequence homology data. For many studies being able to establish whether mitochondria function has been altered or not, is key to understanding whether bioenergetic changes are a cause or consequence of the observed phenotype.

Peroccchi et al¹ leveraged data from comparative physiology, including OXPHOS studies, evolutionary genomics, organelle proteomics, and RNA interference studies to identify a product of CBARA1 gene as the founding member of a set of proteins required for high-capacity mitochondrial calcium uptake. Named MICU1 by the investigators, this gene product is associated with the mitochondrial inner membrane, and has several characteristics required for Ca²⁺ transport, including the two canonical EF hands essential for activity.