Transferred mitochondria accumulate reactive oxygen species, promoting proliferation.

Transferred mitochondria accumulate reactive oxygen species, promoting proliferation.
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转移的线粒体积累活性氧,促进增殖。

DOI:
10.7554/elife.85494
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发表时间:
2023-03-06
期刊:
影响因子:
7.7
通讯作者:
Roh-Johnson M
Roh-Johnson M
中科院分区:
生物学1区
文献类型:
--
作者:
Kidwell CU;Casalini JR;Pradeep S;Scherer SD;Greiner D;Bayik D;Watson DC;Olson GS;Lathia JD;Johnson JS;Rutter J;Welm AL;Zangle TA;Roh-Johnson M

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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.
DOI: 10.1002/cpz1.514
发表时间: 2022-08
期刊: Current protocols
影响因子: --
作者:
Greiner, Daniel;Scott, Tiana M;Olson, Gregory S;Aderem, Alan;Roh-Johnson, Minna;Johnson, Jarrod S
通讯作者: Johnson, Jarrod S