Mitochondrial fission

Mitochondrial fission

Mitochondrial network (green) in two human cells (HeLa cells)

Although commonly depicted as bean-like structures mitochondria form a highly dynamic network within most cells where they constantly undergo fission and fusion. Mitochondria can divide by prokaryotic binary fission and since they require mitochondrial DNA for their function, fission is coordinated with DNA replication. Some of the proteins that are involved in mitochondrial fission have been identified and some of them are associated with mitochondrial diseases.[1]Mitochondrial fission has significant implications in stress response and apoptosis.[2]

Mechanism

The Drp1 protein is a member of the dynamin family of large GTPases. Drp1 controls the final part of mitochondrial fission, pinching off the membrane stalk between two forming daughter mitochondria. The MFN2 protein is part of a complex that links the endoplasmic reticulum (ER) to mitochondria. Points of ER-mitochondrial association have been associated with the formation of Drp1 complexes and mitochondrial fission.[3]

Several Drp1-binding proteins have been identified.[4] A protein called mitochondrial fission factor (Mff) binds Drp1 and promotes mitochondrial fission.[5] The FIS1 protein might recruit Drp1 to sites of fission[6] but it might require association with another protein, MIEF1 (coded for by the SMCR7L gene), to promote mitochondrial fission. In contrast, MIEF1 when bound to Drp1 might prevent mitochondrial fission and thus shift the balance towards fusion of mitochondria.[7]

Recent research found that actin polymerization through ER-localized inverted formin 2 (INF2) was required for efficient mitochondrial fission in mammalian cells. INF2 functioned upstream of Drp1. INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction.[8]

Cryo-electron tomography has been able to visualize mitochondrial division in frozen hydrated cells and has led to the suggestion that mitochondria divide by budding.[9]

See also

References

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