The mitochondrial BKCa channel cardiac interactome reveals BKCa association with the mitochondrial import receptor subunit Tom22, and the adenine nucleotide translocator

- 151 mitochondrial BKCa channel protein partners are revealed by proteomics.
- A molecular framework defining BKCa mitochondrial protein relationships is provided.
- Novel partners of BKCa are Tom22 import protein and ANT nucleotide translocator.
- BKCa interaction with ANT is enhanced by the 50 amino acid BKCa splice insert, DEC.
- The BKCa transmembrane domain is required for the interaction with Tom 22 and ANT.

Mitochondrial BKCa channel, mitoBKCa, regulates mitochondria function in the heart but information on its protein partnerships in cardiac mitochondria is missing. A directed proteomic approach discovered the novel interaction of BKCa with Tom22, a component of the mitochondrion outer membrane import system, and the adenine nucleotide translocator (ANT). The expressed protein partners co-immunoprecipitated and co-segregated into mitochondrial fractions in HEK293T cells. The BKCa 50 amino acid splice insert, DEC, facilitated BKCa interaction with ANT. Further, BKCa transmembrane domain was required for the association with both Tom22 and ANT. The results serve as a working framework to understand mitoBKCa import and functional relationships.