Nowadays ambient particulate matter (PM) levels still regularly exceed the guideline values established by World Health Organization in most urban areas. Numerous experimental studies have already demonstrated the airway toxicity of the fine fraction of PM (FP), mainly triggered by oxidative stress-induced airway inflammation. However, only few studies have actually paid close attention to the ultrafine fraction of PM (UFP), which is likely to be more easily internalized in cells and more biologically reactive. Mitochondria are major endogenous sources of reactive oxygen species (ROS) through oxidative metabolism, and coordinate many critical cellular signaling processes. Mitochondria have been often studied in the context of PM toxicity and generally associated with apoptosis activation. However, little is known about the underlying adaptation mechanisms that could occur following exposure at sub-apoptotic doses of ambient PM. Here, normal human bronchial epithelial BEAS-2B cells were acutely or repeatedly exposed to relatively low doses (5 µg.cm⁻²) of FP (PM_2.5-0.18) or quasi-UFP (Q-UFP; PM_0.18) to better access the critical changes in mitochondrial morphology, functions, and dynamics. No significant cytotoxicity nor increase of apoptotic events were reported for any exposure. Mitochondrial membrane potential (ΔΨm) and intracellular ATP content were also not significantly impaired. After cell exposure to sub-apoptotic doses of FP and notably Q-UFP, oxidative phosphorylation was increased as well as mitochondrial mass, resulting in increased production of mitochondrial superoxide anion. Given this oxidative boost, the NRF2-ARE signaling pathway was significantly activated. However, mitochondrial dynamic alterations in favor of accentuated fission process were observed, in particular after Q-UFP vs FP, and repeated vs acute exposure. Taken together, these results supported mitochondrial quality control and metabolism dysfunction as an early lung underlying mechanism of toxicity, thereby leading to accumulation of defective mitochondria and enhanced endogenous ROS generation. Therefore, these features might play a key role in maintaining PM-induced oxidative stress and inflammation within lung cells, which could dramatically contribute to the exacerbation of inflammatory chronic lung diseases. The prospective findings of this work could also offer new insights into the physiopathology of lung toxicity, arguably initiate and/or exacerbate by acutely and rather repeated exposure to ambient FP and mostly Q-UFP.

如今，大多数城市地区的环境颗粒物（PM）水平仍然经常超过世界卫生组织制定的准则值。大量的实验研究已经证明了PM（FP）细颗粒的呼吸道毒性，主要是由氧化应激引起的气道炎症引起的。然而，只有极少的研究实际上密切关注了PM（UFP）的超细级分，它可能更容易被细胞内化并具有更高的生物反应性。线粒体是通过氧化代谢的活性氧（ROS）的主要内源性来源，并协调许多关键的细胞信号传导过程。线粒体经常在PM毒性的背景下进行研究，通常与细胞凋亡激活有关。然而，对于潜在的适应机制，在亚细胞凋亡剂量的环境PM暴露后可能发生的知之甚少。在此，正常人支气管上皮BEAS-2B细胞急性或反复暴露于相对低剂量（5 µg.cm^-2）FP（PM的_2.5-0.18）或准UFP（Q-UFP; PM _0.18）以更好地了解线粒体形态，功能和动力学的关键变化。对于任何暴露都没有报告明显的细胞毒性或凋亡事件的增加。线粒体膜电位（ΔΨm）和细胞内ATP含量也没有明显受损。细胞暴露于亚凋亡剂量的FP（尤其是Q-UFP）后，氧化磷酸化以及线粒体质量增加，从而导致线粒体超氧阴离子的产生增加。在这种氧化作用下，NRF2-ARE信号传导途径被显着激活。然而，观察到线粒体动态变化有利于加剧裂变过程，特别是在Q-UFP与FP以及反复与急性暴露后。在一起 这些结果支持线粒体质量控制和代谢功能障碍，这是一种早期的肺部潜在毒性机制，从而导致缺陷线粒体的积累和增强的内源性ROS生成。因此，这些特征可能在维持PM诱导的氧化应激和肺细胞内炎症中起关键作用，这可能会极大地加剧炎症性慢性肺病。这项工作的前瞻性发现还可以提供对肺毒性生理病理学的新见解，可以说是急性和反复暴露于环境FP和大部分为Q-UFP引发和/或加剧。这些功能可能在维持PM诱导的肺细胞氧化应激和炎症中起关键作用，这可能会严重加剧炎症性慢性肺部疾病。这项工作的前瞻性发现还可以提供对肺毒性生理病理学的新见解，可以说是急性和反复暴露于环境FP和大部分为Q-UFP引发和/或加剧。这些功能可能在维持PM诱导的肺细胞氧化应激和炎症中起关键作用，这可能会严重加剧炎症性慢性肺部疾病。这项工作的前瞻性发现还可以提供对肺毒性生理病理学的新见解，可以说是急性和反复暴露于环境FP和大部分为Q-UFP引发和/或加剧。