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Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view - PubMed

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Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view

Gilad Twig et al. Biochim Biophys Acta. 2008 Sep.

Abstract

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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Figures

Figure 1
Figure 1. A Schematic model of the mitochondrion’s life cycle and the roles of mitochondrial dynamics and autophagy in the segregation of dysfunctional mitochondria

The mitochondrion cyclically shifts between a post fusion state (Network) and a post fission state (Solitary). Fusion is brief and triggers fission. Following a fission event, the daughter mitochondrion may either maintain intact membrane potential (red line), or depolarize (green line). If it depolarizes, it is unlikely to re-engage in further fusion events for the entire depolarization interval. In the case mitochondrial depolarization is transient and Δψm resumes, fusion capacity is restored (green to red short arrows). However, if Δψm depolarization is sustained, reduction in OPA1 follows and elimination by autophagy occurs.

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