Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta

Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA, USA.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 09/2008; 1777(9):1092-7. DOI: 10.1016/j.bbabio.2008.05.001
Source: PubMed


The mitochondrial life cycle consists of frequent fusion and fission events. Ample experimental and clinical data demonstrate that inhibition of either fusion or fission results in deterioration of mitochondrial bioenergetics. While fusion may benefit mitochondrial function by allowing the spreading of metabolites, protein and DNA throughout the network, the functional benefit of fission is not as intuitive. Remarkably, studies that track individual mitochondria through fusion and fission found that the two events are paired and that fusion triggers fission. On average each mitochondrion would go though approximately 5 fusion:fission cycles every hour. Measurement of Deltapsi(m) during single fusion and fission events demonstrates that fission may yield uneven daughter mitochondria where the depolarized daughter is less likely to become involved in a subsequent fusion and is more likely to be targeted by autophagy. Based on these observations we propose a mechanism by which the integration of mitochondrial fusion, fission and autophagy forms a quality maintenance mechanism. According to this hypothesis pairs of fusion and fission allow for the reorganization and sequestration of damaged mitochondrial components into daughter mitochondria that are segregated from the networking pool and then becoming eliminated by autophagy.

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Available from: Gilad Twig
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    • "Another possible factor causing heterogeneity in mitochondrial content is the dynamics of mitochondrial biogenesis , which is characterized by continuous cycles of fusion and fission. However, these processes are fast compared to the cell-cycle period: on average, each mitochondrion undergoes around 5 fusion:fission cycles per hour[72], and this will likely promote a " steady " population of mitochondria inside the cell[72,73]. It is interesting to note that mitochondrial fusion and fission dynamics are regulated during the cell cycle[74], with mitochondrial fission enhanced during mitosis, which could facilitate passive and stochastic segregation of mitochondria to daughter cells. "
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    • "Ongoing fusion and fission of mitochondria is a prerequisite for the elimination of damaged mitochondria by mitophagy. After a fission event, daughter mitochondria frequently show different polarization states in terms of membrane potential (Twig et al. , 2008 ). It is not elucidated, though, whether fission specifically occurs at functionally impaired sites to separate these parts from the rest of the mitochondrion (Figure 4B). "

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