Sharma Shikha, Wang Qixin, Muthumalage Thivanka, Rahman Irfan
Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Pathophysiology. 2021 Nov 26;28(4):501-512. doi: 10.3390/pathophysiology28040033.
Mitochondrial quality control is sustained by Miro1 (Rhot1), a calcium-binding membrane-anchored GTPase during mitophagy. The exact mechanism that operates the interaction of Miro1 with mitophagy machinery and their role in cigarette smoke (CS)-induced mitochondrial dysfunction that often results in lung inflammation is unclear. We hypothesized that Miro1 plays an important role in regulating mitophagy machinery and the resulting lung inflammation by CS exposure to mice. The lung epithelial Rhot1 (WT) and Rhot1 mice were exposed to mainstream CS for 3 days (acute) and 4 months (chronic). Acute CS exposure showed a notable increase in the total inflammatory cells, macrophages, and neutrophils that are associated with inflammatory mediators. Chronic exposure showed increased infiltration of neutrophils versus air controls. The effects of acute and chronic CS exposure were augmented in the Rhot1 group, indicating that epithelial Miro1 ablation led to the augmentation of inflammatory cell infiltration with alteration in the inflammatory mediators. Thus, Rhot1/Miro1 plays an important role in regulating CS-induced lung inflammatory responses with implications in mitochondrial quality control.
线粒体质量控制由Miro1（Rhot1）维持，Miro1是一种在有丝分裂自噬过程中与钙结合的膜锚定GTP酶。Miro1与有丝分裂自噬机制相互作用的确切机制以及它们在香烟烟雾（CS）诱导的线粒体功能障碍（常导致肺部炎症）中的作用尚不清楚。我们假设Miro1在调节有丝分裂自噬机制以及通过让小鼠暴露于CS而导致的肺部炎症中起重要作用。将肺上皮Rhot1（野生型）和Rhot1基因敲除小鼠暴露于主流香烟烟雾中3天（急性）和4个月（慢性）。急性香烟烟雾暴露显示与炎症介质相关的总炎症细胞、巨噬细胞和中性粒细胞显著增加。慢性暴露显示与空气对照组相比中性粒细胞浸润增加。急性和慢性香烟烟雾暴露的影响在Rhot1基因敲除组中增强，表明上皮Miro1缺失导致炎症细胞浸润增加以及炎症介质改变。因此，Rhot1/Miro1在调节香烟烟雾诱导的肺部炎症反应中起重要作用，这与线粒体质量控制有关。
