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, Oct 10, 2015
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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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    • "Defects in mitochondrial dynamics that result in respiratory chain impairment underlie Parkinson's disease (Kim et al. 2007; Twig et al. 2008; Westermann 2010; Amo et al. 2011). Mitophagy selectively removes a single deleterious mitochondrion (which is discussed later) (Westermann 2010), separating damaged from healthy mitochondria (Twig et al. 2008). Damaged/depolarized/reactive oxygen species (ROS) producing mitochondria are marked by externalized cardiolipin and surface ubiquitination, recognized by PINK1-Parkin and removed by mitophagy (Nunnari and Suomalainen 2012; Ji et al. 2012). "
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    • "Mitochondrial fusion and fission are dynamic processes that regulate the morphology, distribution, function and turnover of those organelles (Twig et al., 2008). Mutations in mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1), two proteins driving mitochondrial outer and inner membrane fusion are associated with the neurodegenerative diseases Charcot- Marie-Tooth type 2A and dominant optic atrophy, respectively (Alexander et al., 2000; Delettre et al., 2000). "
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