ER-mitochondria contacts promote mtDNA nucleoids active transportation via mitochondrial dynamic tubulation

Jinshan Qin, Yuting Guo, Boxin Xue, Peng Shi, Yang Chen, Qian Peter Su, Huiwen Hao, Shujuan Zhao, Congying Wu, Li Yu, Dong Li () and Yujie Sun ()
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Jinshan Qin: Peking University
Yuting Guo: Institute of Biophysics, Chinese Academy of Sciences
Boxin Xue: Peking University
Peng Shi: Peking University
Yang Chen: Peking University
Qian Peter Su: Peking University
Huiwen Hao: Peking University
Shujuan Zhao: Peking University
Congying Wu: Peking University
Li Yu: Tsinghua University
Dong Li: Institute of Biophysics, Chinese Academy of Sciences
Yujie Sun: Peking University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract A human cell contains hundreds to thousands of mitochondrial DNA (mtDNA) packaged into nucleoids. Currently, the segregation and allocation of nucleoids are thought to be passively determined by mitochondrial fusion and division. Here we provide evidence, using live-cell super-resolution imaging, that nucleoids can be actively transported via KIF5B-driven mitochondrial dynamic tubulation (MDT) activities that predominantly occur at the ER-mitochondria contact sites (EMCS). We further demonstrate that a mitochondrial inner membrane protein complex MICOS links nucleoids to Miro1, a KIF5B receptor on mitochondria, at the EMCS. We show that such active transportation is a mechanism essential for the proper distribution of nucleoids in the peripheral zone of the cell. Together, our work identifies an active transportation mechanism of nucleoids, with EMCS serving as a key platform for the interplay of nucleoids, MICOS, Miro1, and KIF5B to coordinate nucleoids segregation and transportation.

Date: 2020
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DOI: 10.1038/s41467-020-18202-4

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