Mitochondrial fission and fusion dynamics: the long and short of it

Abstract

Maintenance of functional mitochondria requires fusion and fission of these dynamic organelles. The proteins that regulate mitochondrial dynamics are now associated with a broad range of cellular functions. Mitochondrial fission and fusion are often viewed as a finely tuned balance within cells, yet an integrated and quantitative understanding of how these processes interact with each other and with other mitochondrial and cellular processes is not well formulated. Direct visual observation of mitochondrial fission and fusion events, together with computational approaches promise to provide new insight.

Figure 1

Yeast proteins required for normal mitochondrial morphology through their direct or indirect roles; for more information and citations, see Saccharomyces Genome Database at http://www.yeastgenome.org

Figure 2

When the equilibrium between mitochondrial fission and fusion is reset to yield longer, more connected mitochondrial morphology, detected here in mammalian cells with mitoGFP, there are a number of potential mechanisms, or combinations of mechanisms to explain this altered morphology

Figure 3

Monitoring mitochondrial movement. Time-lapse imaging was performed on a 14-day culture of primary rat cortical neurons cotransfected with mitochondrially targeted RFP and photoactivatable GFP; one mitochondrion was photoactivated (yellow). Blue arrows track the movement of an RFP-labeled mitochondrion past the photoactivated mitochondrion. Under RFP fluorescence detection alone, one cannot distinguish the monitored (red) and the photoactivated mitochondrion when both are juxtaposed, and it cannot be determined whether these mitochondria fuse. Using photoactivatable GFP, it can be concluded that these two mitochondria fail to fuse their matrices, even though they spend several minutes next to each other. Time 0 is at 8 min and 40 s from the start of a 15 min observation period

Figure 4

Quantifying mitochondrial fission and fusion. Consider a volume containing 10 mitochondria in which, on average, there is one fission event and one fusion event per a fixed time interval. If one of the 10 mitochondria is randomly selected for photoactivation, then one is twice as likely to activate a mitochondrion that will undergo a fusion event (p_fussion=2/10) during the observation period, than one is likely to select a mitochondrion that will undergo a fission event (p_fussion=1/10). Thus, one will observe twice as many fusion events as fission events, even though the number of fission events equals the number of fusion events