Proton leak pathways uncouple substrate oxidation from ATP synthesis in mitochondria. These pathways are classified as basal (not regulated) or inducible (activated and inhibited). Previously it was found that over half of the basal proton conductance of muscle mitochondria was catalyzed by the adenine nucleotide translocase (ANT), an abundant mitochondrial anion carrier protein. To determine whether ANT is the unique protein catalyst, or one of many proteins that catalyze basal proton conductance, we measured proton leak kinetics in mitochondria isolated from brown adipose tissue (BAT). BAT can express another mitochondrial anion carrier, UCP1, at concentrations similar to ANT. Basal proton conductance was measured under conditions where UCP1 and ANT were catalytically inactive and was found to be lower in mitochondria from UCP1 knockout mice compared to wild-type. Ablation of another abundant inner membrane protein, nicotinamide nucleotide transhydrogenase, had no effect on proton leak kinetics in mitochondria from liver, kidney or muscle, showing that basal proton conductance is not catalyzed by all membrane proteins. We identify UCP1 as a second protein propagating basal proton leak, lending support to the hypothesis that basal leak pathways are perpetrated by members of the mitochondrial anion carrier family but not by other mitochondrial inner membrane proteins.

中文翻译：

---

解偶联蛋白-1 (UCP1) 有助于棕色脂肪组织线粒体的基础质子传导。

质子泄漏途径将底物氧化与线粒体中的 ATP 合成分离。这些途径被分类为基础的（不受调节的）或诱导的（激活的和抑制的）。以前发现，超过一半的肌肉线粒体基础质子传导是由腺嘌呤核苷酸转位酶 (ANT) 催化的，这是一种丰富的线粒体阴离子载体蛋白。为了确定 ANT 是独特的蛋白质催化剂，还是许多催化基础质子电导的蛋白质之一，我们测量了从棕色脂肪组织 (BAT) 分离的线粒体中的质子泄漏动力学。BAT 可以以类似于 ANT 的浓度表达另一种线粒体阴离子载体 UCP1。在 UCP1 和 ANT 催化失活的条件下测量基础质子电导，发现与野生型相比，UCP1 基因敲除小鼠的线粒体中的基础质子电导较低。另一种丰富的内膜蛋白烟酰胺核苷酸转氢酶的消融对肝脏、肾脏或肌肉线粒体中的质子泄漏动力学没有影响，表明基础质子电导并非由所有膜蛋白催化。我们将 UCP1 确定为传播基底质子泄漏的第二种蛋白质，支持了基底泄漏途径由线粒体阴离子载体家族成员而不是其他线粒体内膜蛋白实施的假设。对来自肝脏、肾脏或肌肉的线粒体中的质子泄漏动力学没有影响，表明基础质子电导并非由所有膜蛋白催化。我们将 UCP1 确定为传播基底质子泄漏的第二种蛋白质，支持了基底泄漏途径由线粒体阴离子载体家族成员而不是其他线粒体内膜蛋白实施的假设。对来自肝脏、肾脏或肌肉的线粒体中的质子泄漏动力学没有影响，表明基础质子电导并非由所有膜蛋白催化。我们将 UCP1 确定为传播基底质子泄漏的第二种蛋白质，支持了基底泄漏途径由线粒体阴离子载体家族成员而不是其他线粒体内膜蛋白实施的假设。