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. 2012;7(5):e19879.
doi: 10.1371/journal.pone.0019879. Epub 2012 May 23.

Multi-patterned dynamics of mitochondrial fission and fusion in a living cell

Shiqi Wang  1 , Weiming Xiao, Sicong Shan, Chunsun Jiang, Ming Chen, Yan Zhang, Shouqin Lü, Juan Chen, Chuanmao Zhang, Quan Chen, Mian Long
Affiliations

Multi-patterned dynamics of mitochondrial fission and fusion in a living cell

Shiqi Wang et al. PLoS One. 2012.

Abstract

Mitochondria are highly-dynamic organelles, but it is challenging to monitor quantitatively their dynamics in a living cell. Here we developed a novel approach to determine the global occurrence of mitochondrial fission and fusion events in living human epithelial cells (Hela) and mouse embryonic fibroblast cells (MEF). Distinct patterns of sequential events including fusion followed by fission (Fu-Fi), the so-called "kiss and run" model previously described, fission followed by fusion (Fi-Fu), fusion followed by fusion (Fu-Fu), and fission followed by fission (Fi-Fi) were observed concurrently. The paired events appeared in high frequencies with short lifetimes and large sizes of individual mitochondria, as compared to those for unpaired events. The high frequencies of paired events were found to be biologically significant. The presence of membrane uncoupler CCCP enhanced the frequency of paired events (from both Fu-Fi and Fi-Fu patterns) with a reduced mitochondrial size. Knock-out of mitofusin protein Mfn1 increased the frequency of fission with increased lifetime of unpaired events whereas deletion of both Mfn1 and Mfn2 resulted in an instable dynamics. These results indicated that the paired events were dominant but unpaired events were not negligible, which provided a new insight into mitochondrial dynamics. In addition to kiss and run model of action, our data suggest that, from a global visualization over an entire cell, multiple patterns of action appeared in mitochondrial fusion and fission.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Mitochondrial evolution in a living Hela cell.
A global roadmap of mitochondrial evolution was presented up to 450 s (A) for an entire Hela cell (B) where distinct mitochondria were denoted as numbers in different colored boxes. Time-lapsed images obtained from a dual-photon laser scanning microscopy were illustrated at t = 345 (C), 360 (D), 375 (E), and 390 (F) s for those typical mitochondria located at right lower region of the cell (black box in A and blue box in B) and colored with numbers. Also plotted were merged images at two sequential time points where all the mitochondria were colored as red (R) at a given point and as green (G) at the following point (G–I). Bar = 2 µm.
Figure 2
Figure 2. Sequential events of mitochondrial fission and fusion in a Hela or MEF cell.
Time-lapsed images were employed to illustrate four patterns of sequential events of mitochondrial fission and fusion in a Hela (1st–4th rows) or a MEF (5th–8th rows) cell, that is, fusion followed by fission (Fu-Fi, 1st and 5th rows), fission followed by fusion (Fi-Fu, 2nd and 6th rows), fusion followed by fusion (Fu-Fu, 3rd and 7th rows), and fission followed by fission (4th and 8th rows), at t = 0 (1st column), 15 (2nd column), 30 (3rd column), 45 (4th column), and 60 (5th column) s. In the panels, an isolated mitochondrial was colored as red, green, or blue, and arrows denoted as a fission event and arrow heads indicated a fusion event. Also plotted were merged images at three sequential time points where all the mitochondria were colored as red (R) at a given point, as green (G) at the following point, and as blue (B) at the last point (6th and 7th columns). Bar = 1 µm.
Figure 3
Figure 3. Schematic of different dynamic patterns of mitochondrial fission and fusion.
Definitions of hetero- (A, B), homo- (C, D) triggered patterns and of paired or unpaired events (A–D). Here a letter was denoted as a mitochondrion and a number was referred to an event.
Figure 4
Figure 4. Multi-dynamic patterns in a Hela or MEF cell or from simulations.
Comparisons of occurrence frequency of distinct patterns in a Hela (A) and fraction of paired and unpaired events (B) in a Hela (open bars) or MEF (hatched bars) cell as well as from Monte-Carlo simulations (solid bars). Also plotted were the time courses of accumulative frequency of paired (Pd) or unpaired (UPd) fission (Fi) and fusion (Fu) events in a Hela (C) or MEF (D) cell up to t = 285 s. Data were presented as mean ± standard error (SE) measured from total 21–43 mitochondria and 121–231 events per cell.
Figure 5
Figure 5. Multi-dynamic patterns in an intact or treated Hela cell.
Comparisons of occurrence frequency of distinct patterns (A) and fraction of paired and unpaired events (B) in an intact (open bars), CCCP-treated (hatched bars), and nocodazole-treated (solid bars) Hela cell. Also plotted were the time courses of accumulative frequency of paired (Pd) or unpaired (UPd) fission (Fi) and fusion (Fu) events in a CCCP-treated (C) or nocodazole-treated (D) Hela cell up to t = 285 s. Data were presented as mean ± standard error (SE) measured from total 21–63 mitochondria and 121–216 events per cell.
Figure 6
Figure 6. Multi-dynamic patterns in a wild-type or mutated MEF cell.
Comparisons of occurrence frequency of distinct patterns (A) and fraction of paired and unpaired events (B) in a MEF-WT (open bars), MEF Mfn1 −/− (hatched bars), and MEF Mfn1&2 −/− (solid bars) cell. Also plotted were the time courses of accumulative frequency of paired (Pd) or unpaired (UPd) fission (Fi) and fusion (Fu) events in a MEF Mfn1 −/− (C) or MEF Mfn1&2 −/− (D) cell up to t = 285 s. Data were presented as mean ± standard error (SE) measured from total 16–65 mitochondria and 26–231 events per cell.
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