Multi-patterned dynamics of mitochondrial fission and fusion in a living cell.
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.
Key Laboratory of Microgravity (National Microgravity Laboratory), Chinese Academy of Sciences, Beijing, China.
Shiqi
S
Wang
Weiming
W
Xiao
Sicong
S
Shan
Chunsun
C
Jiang
Ming
M
Chen
Yan
Y
Zhang
Shouqin
S
Lü
Juan
J
Chen
Chuanmao
C
Zhang
Quan
Q
Chen
Mian
M
Long
D000818:Animals; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000378:metabolism*; D005347:Fibroblasts; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006367:HeLa Cells; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method
D033681:Mitochondrial Membrane Transport Proteins; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D020558:GTP Phosphohydrolases; C470017:Mfn1 protein, human