title: Dynamic tubulation of mitochondria drives mitochondrial network formation.
abstract: Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, whereas disruption of the mitochondrial network affects mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. Here, we report a new mechanism for formation of mitochondrial networks through KIF5B-mediated dynamic tubulation of mitochondria. We found that KIF5B pulls thin, highly dynamic tubules out of mitochondria. Fusion of these dynamic tubules, which is mediated by mitofusins, gives rise to the mitochondrial network. We further demonstrated that dynamic tubulation and fusion is sufficient for mitochondrial network formation, by reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5B, and polymerized microtubules. Interestingly, KIF5B only controls network formation in the peripheral zone of the cell, indicating that the mitochondrial network is divided into subzones, which may be constructed by different mechanisms. Our data not only uncover an essential mechanism for mitochondrial network formation, but also reveal that different parts of the mitochondrial network are formed by different mechanisms.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Du
authors.affiliation: State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), Beijing 100871, China.|School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Qian Peter
authors.initials: QP
authors.lastname: Su
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Mathematical Science Center, Tsinghua University, Beijing 100084, China.
authors.forename: Yichen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Na
authors.initials: N
authors.lastname: Mi
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yueyao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Jiang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Senyan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zerui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), Beijing 100871, China.|School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University-Peking University Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.|School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D002460:Cell Line; D020558:GTP Phosphohydrolases; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000378:metabolism; D051381:Rats
chemical_list: C521566:KIF5B protein, rat; D008565:Membrane Proteins; C489709:Mfn1 protein, rat; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; C489710:Mfn2 protein, rat; D016547:Kinesins