Dynamic Tubulation Of Mitochondria Drives Mitochondrial Network Formation

Mitochondria form networks. Formation of mitochondrial networks is important for maintaining mitochondrial DNA integrity and interchanging mitochondrial material, and disruption of the mitochondrial network affects many mitochondrial functions. According to the current view, mitochondrial networks are formed by fusion of individual mitochondria. In this manuscript, we report that KIF5B-mediated dynamic tubulation of mitochondria is an additional mechanism for formation of the mitochondrial network. We found that KIF5 B 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, as we succeeded in reconstituting mitochondrial networks in vitro using purified fusion-competent mitochondria, recombinant KIF5 B, and polymerized microtubules. Interestingly, KIF5 B 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.