[show abstract][hide abstract] ABSTRACT: Mitochondrial iron levels are tightly regulated, as iron is essential for the synthesis of Fe/S clusters and heme in the mitochondria, but high levels can cause oxidative stress. The ATP-binding cassette (ABC) transporter ABCB8 is a mitochondrial inner membrane protein with an unknown function. Here, we show that ABCB8 is involved in mitochondrial iron export and is essential for baseline cardiac function. Induced genetic deletion of ABCB8 in mouse hearts resulted in mitochondrial iron accumulation and cardiomyopathy, as assessed by echocardiography and invasive hemodynamics. Mice with ABCB8 deletion in the heart also displayed mitochondrial damage, and higher levels of reactive oxygen species and cell death. Down-regulation of ABCB8 in vitro resulted in decreased iron export from isolated mitochondria, whereas its overexpression had the opposite effect. Furthermore, ABCB8 is needed for the maturation of the cytosolic Fe/S proteins, as its deletion in vitro and in vivo led to decreased activity of cytosolic, but not mitochondrial, iron-sulfur-containing enzymes. These results indicate that ABCB8 is essential for normal cardiac function, maintenance of mitochondrial iron homeostasis and maturation of cytosolic Fe/S proteins. In summary, this report provides characterization of a protein involved in mitochondrial iron export.
Proceedings of the National Academy of Sciences 02/2012; 109(11):4152-7. · 9.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Introduction
Suspensory femoral fixation is commonly used for soft-tissue graft ACL reconstruction. For this fixation to be utilized, it is considered imperative that the lateral femoral cortex is not violated. Anatomic, single and double-bundle femoral tunnel techniques lead to shorter tunnels and, thus, are susceptible to an increased incidence of cortical breaching, or “blowout.” When this occurs, it is assumed a secondary type of fixation is needed. The purpose of our study was to determine if secondary fixation is needed when femoral “blowout” occurs, and whether the diameter of the femoral tunnel affects the cyclical and ultimate load to failure of three different suspensory fixation devices.
Sixty fresh-frozen porcine femora were dissected to isolate the ACL footprint. Femoral ACL tunnels were then drilled at 7-, 8-, 9-, and 10-mm diameters. Biomechanical testing, both cyclical and load to failure, were undertaken utilizing an MTS machine. Five separate trials at each tunnel diameter were conducted for three different cortical suspension devices. Statistical analysis was then performed to compare the methods of failures and forces to failure across the four tunnel diameters, as well as the three devices.
Mean load-to-failure decreased as the tunnel size enlarged for all three devices. In 7-mm tunnels, mean load-to-failure ranged from 1163.7 to 1455.0 N; in 8-mm tunnels, 1154.7 to 1643.2 N; in 9-mm tunnels, 820.8 to 1125.21 N; and in 10-mm tunnels, 314.7 to 917.8 N, across the three devices. No significant difference was seen with the mean load-to-failure between the three devices (p<0.52). Methods of failure also varied as the tunnel sizes enlarged. In the 7- and 8-mm tunnels there were no failures across the three devices during cyclical testing, or with the devices being pulled into the tunnel; all the failures were due to the devices either mechanically failing, or by subsiding through the cortex of the bone. With 9- and 10-mm tunnels there were failures both during cyclical testing and with the devices being pulled into the tunnel, thus the larger range of ultimate load values. Significant failure forces (N) were seen in the three devices in the following failure modes, independent of the tunnel diameter: device pulling into bone (p<0.002), device/loop interface breaking (p<0.002), and device breaking (p<0.001). Also, statistical significance was seen between the failure forces (N), in each tunnel diameter with the following failure modes, independent of the device: device/loop interface breaking (p<0.003), cyclical testing (p<0.001), device pulled into tunnel (p<0.01), and device breaking (p<0.001).
When using suspensory fixation, secondary fixation is not always needed when the lateral cortex has been breached. With 7-mm and 8-mm diameter tunnels, failure loads with each of the suspensory devices tested, exceeded that of documented interference screw load to failure (an accepted means of soft tissue fixation) by at least 25%. In pediatric and double-bundle ACL reconstructions where smaller and shorter tunnels are routinely used, purposely breaching the lateral cortex when using suspensory fixation, is an acceptable technique to optimize tunnel length, while still achieving stable fixation.
Arthroscopy The Journal of Arthroscopic and Related Surgery 27(5):e64–e65. · 3.10 Impact Factor