mABC2 (ABCB10) protein is a mitochondrial inner-membrane ATP-binding cassette transporter. The structure of mABC2 is similar to that of ABCB8 ... Show moremABC2 (ABCB10) protein is a mitochondrial inner-membrane ATP-binding cassette transporter. The structure of mABC2 is similar to that of ABCB8 (mABC1), which was shown to export iron from mitochondria into the cytoplasm. Based on the structural similarities we hypothesized that mABC2 is involved in export of heme from mitochondria into the cytoplasm for subsequent use in cytosolic enzymes. To study the role of mABC2 in cellular and mitochondrial iron homeostasis, we modulated the expression of the protein in neonatal rat cardiomyocytes (NRCM). We found that downregulation of mABC2 led to significant decrease in total cellular heme content. There was a trend toward increase in total cellular heme content with overexpression of mABC2, however the finding was not statistically significant (p=0.36). To measure mitochondrial heme content with mABC2 modulation we have successfully isolated mitochondria from NRCM. Overexpression of mABC2 significantly elevated mitochondrial heme content. It has been shown that mABC2 and mitoferrin-1 (Mfrn1) interact and form an oligomeric complex with ferrochelates to enhance mitochondrial iron importation for heme biosynthesis. Our findings are inconsistent with the proposed function of mABC2 in heme export out of the mitochondria, but support the hypothesis that mABC2 modulates heme synthesis via regulation of stability and activity of Mfrn1 and ferrochelatase in cardiomyocytes. This suggests that mABC2 may play a role in regulation of cellular iron homeostasis by regulating expression of cellular iron import and/or export. M.S. in Biology, May 2011 Show less
