The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission results in deterioration of mitochondrial bioenergetics. While fusion may benefit mitochondrial function by allowing the spreading of metabolites, protein and DNA throughout the network, the functional benefit of fission is not as intuitive. Remarkably, studies that track individual mitochondria through fusion and fission found that the two events are paired and that fusion triggers fission. On average each mitochondrion would go though approximately 5 fusion:fission cycles every hour. Measurement of Deltapsi(m) during single fusion and fission events demonstrates that fission may yield uneven daughter mitochondria where the depolarized daughter is less likely to become involved in a subsequent fusion and is more likely to be targeted by autophagy. Based on these observations we propose a mechanism by which the integration of mitochondrial fusion, fission and autophagy forms a quality maintenance mechanism. According to this hypothesis pairs of fusion and fission allow for the reorganization and sequestration of damaged mitochondrial components into daughter mitochondria that are segregated from the networking pool and then becoming eliminated by autophagy.

Mitoferrin-1 (Mfrn1; Slc25a37), a member of the solute carrier family localized in the mitochondrial inner membrane, functions as an essential iron importer for the synthesis of mitochondrial heme and iron-sulfur clusters in erythroblasts. The biochemistry of Mfrn1-mediated iron transport into the mitochondria, however, is poorly understood. Here, we used the strategy of in vivo epitope-tagging affinity purification and mass spectrometry to investigate Mfrn1-mediated mitochondrial iron homeostasis. Abcb10, a mitochondrial inner membrane ATP-binding cassette transporter highly induced during erythroid maturation in hematopoietic tissues, was found as one key protein that physically interacts with Mfrn1 during mouse erythroleukemia ( Abcb transporters ͉ erythropoiesis ͉ iron and heme metabolism ͉ solute carriers ͉ protein complexes

Background Oxidative stress and mitochondrial dysfunction are central mediators of cardiac dysfunction following ischemia-reperfusion. ABC-me (ABCB10/mABC2) is a mitochondrial transporter highly induced during erythroid differentiation and predominantly expressed in bone marrow, liver and heart. However, ABC-me function in heart is unknown. Several lines of evidence demonstrate that the yeast orthologue of ABC-me protects from increased oxidative stress. Therefore, ABC-me is a potential modulator of the outcome of ischemia-reperfusion in the heart. Methods and results Mice harboring one functional allele of ABC-me (ABC-me +/-) were generated by replacing ABC-me exons 2 and 3 by a neomycin resistance cassette. Cardiac function was assessed using Langendorff perfusion and echocardiography. Under basal conditions, ABC-me +/- mice had normal heart structure, hemodynamic function, mitochondrial respiration and oxidative status. However, following ischemia-reperfusion, the recovery of hemodynamic function was reduced by 50% in ABC-me +/- hearts due to impairments in both systolic and diastolic function. This reduction was associated with impaired mitochondrial bioenergetic function and with oxidative damage to both mitochondrial lipids and the sarcoplasmic reticulum calcium ATPase (SERCA) after reperfusion. Treatment of ABC-me +/- hearts with the superoxide dismutase/catalase mimetic EUK-207 prevented oxidative damage to mitochondria and SERCA, and restored mitochondrial and cardiac function to wild type levels after reperfusion. Conclusions Inactivation of one allele of ABC-me increases the susceptibility to oxidative stress induced by ischemia-reperfusion, leading to increased oxidative damage to mitochondria and SERCA, and to impaired functional recovery. Thus, ABC-me is a novel gene that determines the ability to tolerate cardiac ischemia-reperfusion.