Tracking the formation and degradation of fatty-acid-accumulated mitochondria using label-free chemical imaging.
Tracking the formation and degradation of fatty-acid-accumulated mitochondria using label-free chemical imaging.
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DOI：
10.1038/s41598-021-85795-1
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发表时间：
2021-03-23
影响因子：
4.6
通讯作者：
Boppart SA
中科院分区：
文献类型：
--
作者：
Zhang C;Boppart SA
线粒体是维持细胞内环境稳定的关键细胞器之一。外部环境刺激和内部调节过程可以改变线粒体的代谢和功能。为了了解线粒体的这些活动，探测这些细胞器内的关键代谢分子至关重要。在这项研究中，我们使用无标记的化学成像模式，包括相干反斯托克斯拉曼散射和多光子激发荧光研究活癌细胞中的线粒体活动。我们发现，低温暴露倾向于诱导脂肪酸（FA）积累在MIAPaCa-2细胞的一些线粒体。自体荧光图像显示，FA积累的线粒体也具有烟酰胺腺嘌呤二核苷酸氢的异常代谢，可能是由电子传递链的功能障碍引起的。我们还发现，当细胞在一段时间的低温后重新升温到生理温度时，FA积累的线粒体改变了它们的结构特征。据我们所知，这是第一次在活细胞中观察到线粒体中的FA积累。我们的研究还表明，多模式无标记化学成像是一个有吸引力的工具，发现异常功能的线粒体在单个细胞器的水平，并可用于量化这些细胞器在扰动条件下的动态变化。
The mitochondrion is one of the key organelles for maintaining cellular homeostasis. External environmental stimuli and internal regulatory processes may alter the metabolism and functions of mitochondria. To understand these activities of mitochondria, it is critical to probe the key metabolic molecules inside these organelles. In this study, we used label-free chemical imaging modalities including coherent anti-Stokes Raman scattering and multiphoton-excited fluorescence to investigate the mitochondrial activities in living cancer cells. We found that hypothermia exposure tends to induce fatty-acid (FA) accumulation in some mitochondria of MIAPaCa-2 cells. Autofluorescence images show that the FA-accumulated mitochondria also have abnormal metabolism of nicotinamide adenine dinucleotide hydrogen, likely induced by the dysfunction of the electron transport chain. We also found that when the cells were re-warmed to physiological temperature after a period of hypothermia, the FA-accumulated mitochondria changed their structural features. To the best of our knowledge, this is the first time that FA accumulation in mitochondria was observed in live cells. Our research also demonstrates that multimodal label-free chemical imaging is an attractive tool to discover abnormal functions of mitochondria at the single-organelle level and can be used to quantify the dynamic changes of these organelles under perturbative conditions.
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影响因子：
3.6
作者：
Jones, Gareth W.;Marks, Daniel L.;Boppart, Stephen A.
通讯作者：
Boppart, Stephen A.
影响因子：
7.4
作者：
Chowdary, Praveen D.;Benalcazar, Wladimir A.;Gruebele, Martin
通讯作者：
Gruebele, Martin
影响因子：
2.5
作者：
Langbein, Wolfgang;Rocha-Mendoza, Israel;Borri, Paola
通讯作者：
Borri, Paola
影响因子：
3.3
作者：
Fu, Dan;Holtom, Gary;Freudiger, Christian;Zhang, Xu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney
影响因子：
4
作者：
Marks, DL;Vinegoni, C;Boppart, SA
通讯作者：
Boppart, SA