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H 转运是线粒体 ADP/ATP 载体的一个基本功能。

H transport is an integral function of the mitochondrial ADP/ATP carrier.

机构信息

Department of Physiology, University of California San Francisco, San Francisco, CA, USA.

Dana-Farber Cancer Institute & Department of Cell Biology, Harvard Medical School, Boston, MA, USA.

出版信息

Nature. 2019 Jul;571(7766):515-520. doi: 10.1038/s41586-019-1400-3. Epub 2019 Jul 24.

DOI:10.1038/s41586-019-1400-3
PMID:31341297
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6662629/
Abstract

The mitochondrial ADP/ATP carrier (AAC) is a major transport protein of the inner mitochondrial membrane. It exchanges mitochondrial ATP for cytosolic ADP and controls cellular production of ATP. In addition, it has been proposed that AAC mediates mitochondrial uncoupling, but it has proven difficult to demonstrate this function or to elucidate its mechanisms. Here we record AAC currents directly from inner mitochondrial membranes from various mouse tissues and identify two distinct transport modes: ADP/ATP exchange and H transport. The AAC-mediated H current requires free fatty acids and resembles the H leak via the thermogenic uncoupling protein 1 found in brown fat. The ADP/ATP exchange via AAC negatively regulates the H leak, but does not completely inhibit it. This suggests that the H leak and mitochondrial uncoupling could be dynamically controlled by cellular ATP demand and the rate of ADP/ATP exchange. By mediating two distinct transport modes, ADP/ATP exchange and H leak, AAC connects coupled (ATP production) and uncoupled (thermogenesis) energy conversion in mitochondria.

摘要

线粒体 ADP/ATP 载体（AAC）是线粒体内膜的主要转运蛋白。它将线粒体中的 ATP 交换为细胞质中的 ADP，从而控制细胞内 ATP 的产生。此外，有人提出 AAC 介导了线粒体解偶联，但证明这一功能及其机制非常困难。在这里，我们直接从各种小鼠组织的线粒体内部膜记录 AAC 电流，并确定了两种不同的转运模式：ADP/ATP 交换和 H 转运。AAC 介导的 H 电流需要游离脂肪酸，类似于棕色脂肪中发现的解偶联蛋白 1 的 H 渗漏。通过 AAC 的 ADP/ATP 交换负调节 H 渗漏，但不能完全抑制它。这表明 H 渗漏和线粒体解偶联可以通过细胞内 ATP 需求和 ADP/ATP 交换的速率进行动态控制。通过介导 ADP/ATP 交换和 H 渗漏这两种不同的转运模式，AAC 将耦联（ATP 产生）和解耦联（产热）的线粒体能量转换联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8791/6662629/b36201dac811/nihms-1530212-f0005.jpg
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