NOX4-TIM23 interaction regulates NOX4 mitochondrial import and metabolic reprogramming.
NOX4-TIM23 interaction regulates NOX4 mitochondrial import and metabolic reprogramming.
复制标题
NOX 4-TIM 23相互作用调节NOX 4线粒体输入和代谢重编程。
DOI：
10.1016/j.jbc.2023.104695
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发表时间：
2023-05
影响因子：
4.8
通讯作者：
Carter, A. Brent
中科院分区：
文献类型：
--
作者：
Pandey, Jyotsana;Larson-Casey, Jennifer L.;Patil, Mallikarjun H.;Joshi, Rutwij;Jiang, Chun-sun;Zhou, Yong;He, Chao;Carter, A. Brent
肺纤维化是一种以巨噬细胞活化为特征的进行性肺部疾病。石棉诱导肺巨噬细胞表达烟酰胺腺嘌呤二核苷酸磷酸氢氧化酶4(NOX4)，通过产生线粒体活性氧(ROS)，调节线粒体生物发生，促进细胞凋亡抵抗，从而介导纤维化进展；然而，NOX4在纤维化过程中定位于线粒体的机制(S)尚不清楚。在这里，我们展示了NOX4通过与TIM23的直接相互作用定位于石棉暴露后肺巨噬细胞的线粒体基质。在石棉肺患者的肺巨噬细胞中发现了TIM23和NOX4的相互作用，而在肺巨噬细胞中存在条件缺失的NOX4的小鼠中没有TIM23和NOX4的相互作用。这种相互作用定位于NOX4的近端跨膜区。在机制上，TIM23增强了NOX4诱导的线粒体ROS和代谢重编程为氧化磷酸化。沉默TIM23可降低线粒体ROS和氧化磷酸化水平。这些观察结果突显了线粒体转位酶TIM23与NOX4相互作用的重要作用。此外，这种相互作用是肺巨噬细胞线粒体氧化还原信号和代谢重编程所必需的。
Pulmonary fibrosis is a progressive lung disease characterized by macrophage activation. Asbestos-induced expression of nicotinamide adenine dinucleotide phosphate hydrogen oxidase 4 (NOX4) in lung macrophages mediates fibrotic progression by the generation of mitochondrial reactive oxygen species (ROS), modulating mitochondrial biogenesis, and promoting apoptosis resistance; however, the mechanism(s) by which NOX4 localizes to mitochondria during fibrosis is not known. Here, we show that NOX4 localized to the mitochondrial matrix following asbestos exposure in lung macrophages via direct interaction with TIM23. TIM23 and NOX4 interaction was found in lung macrophages from human subjects with asbestosis, while it was absent in mice harboring a conditional deletion of NOX4 in lung macrophages. This interaction was localized to the proximal transmembrane region of NOX4. Mechanistically, TIM23 augmented NOX4-induced mitochondrial ROS and metabolic reprogramming to oxidative phosphorylation. Silencing TIM23 decreased mitochondrial ROS and oxidative phosphorylation. These observations highlight the important role of the mitochondrial translocase TIM23 interaction with NOX4. Moreover, this interaction is required for mitochondrial redox signaling and metabolic reprogramming in lung macrophages.
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DOI：
10.1161/atvbaha.116.308749
发表时间：
2017-03
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Den Hartigh LJ;Omer M;Goodspeed L;Wang S;Wietecha T;O'Brien KD;Han CY
通讯作者：
Han CY
DOI：
10.1165/rcmb.2015-0183oc
发表时间：
2016-07-01
影响因子：
6.4
作者：
He, Chao;Larson-Casey, Jennifer L.;Carter, A. Brent
通讯作者：
Carter, A. Brent
DOI：
10.1096/fj.202100339r
发表时间：
2021-06
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Larson-Casey JL;Gu L;Davis D;Cai GQ;Ding Q;He C;Carter AB
通讯作者：
Carter AB
影响因子：
4.3
作者：
Kamp, DW;Panduri, V;Chandel, N
通讯作者：
Chandel, N
影响因子：
4.8
作者：
He, Chao;Ryan, Alan J.;Carter, A. Brent
通讯作者：
Carter, A. Brent