线粒体
细胞生物学
活性氧
线粒体ROS
生物
生物能学
癌细胞
细胞
重编程
细胞生长
癌症
生物化学
遗传学
作者
Chelsea U. Kidwell,Joseph Casalini,Soorya Pradeep,Sandra D. Scherer,Daniel Greiner,Defne Bayık,Dionysios C. Watson,Gregory S. Olson,Justin D. Lathia,Jarrod S Johnson,Jared Rutter,Alana L. Welm,Thomas A. Zangle,Minna Roh-Johnson
出处
期刊:eLife
[eLife Sciences Publications, Ltd.]
日期:2023-03-06
卷期号:12
被引量:5
摘要
Recent studies reveal that lateral mitochondrial transfer, the movement of mitochondria from one cell to another, can affect cellular and tissue homeostasis. Most of what we know about mitochondrial transfer stems from bulk cell studies and have led to the paradigm that functional transferred mitochondria restore bioenergetics and revitalize cellular functions to recipient cells with damaged or non-functional mitochondrial networks. However, we show that mitochondrial transfer also occurs between cells with functioning endogenous mitochondrial networks, but the mechanisms underlying how transferred mitochondria can promote such sustained behavioral reprogramming remain unclear. We report that unexpectedly, transferred macrophage mitochondria are dysfunctional and accumulate reactive oxygen species in recipient cancer cells. We further discovered that reactive oxygen species accumulation activates ERK signaling, promoting cancer cell proliferation. Pro-tumorigenic macrophages exhibit fragmented mitochondrial networks, leading to higher rates of mitochondrial transfer to cancer cells. Finally, we observe that macrophage mitochondrial transfer promotes tumor cell proliferation in vivo. Collectively these results indicate that transferred macrophage mitochondria activate downstream signaling pathways in a ROS-dependent manner in cancer cells, and provide a model of how sustained behavioral reprogramming can be mediated by a relatively small amount of transferred mitochondria in vitro and in vivo.
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