An Actin-Dependent Step in Mitochondrial Fission Mediated by the ER-Associated Formin INF2
By F. Korobova, Vinay Ramabhadran, H. Higgs. Science, 2013
785 citations recorded by the source corpus.
Masterminding Mitochondrial Fission Mitochondria are highly dynamic and undergo fusion and fission and they move in cells. Defects in mitochondrial dynamics are implicated in many neurodegenerative diseases. Recent findings have suggested that mitochondrial fission occurs preferentially at endoplasmic reticulum (ER) contact sites, with ER circumscribing mitochondria and possibly promoting the constriction of mitochondria during fission. Korobova et al. (p. 464) now suggest that an ER-localized formin, INF2, is required for mitochondrial fission and that INF2-mediated actin polymerization facilitates mitochondrial constriction. Actin filaments between the endoplasmic reticulum and mitochondria promote mitochondrial fission. Mitochondrial fission is fundamentally important to cellular physiology. The dynamin-related protein Drp1 mediates fission, and interaction between mitochondrion and endoplasmic reticulum (ER) enhances fission. However, the mechanism for Drp1 recruitment to mitochondria is unclear, although previous results implicate actin involvement. Here, we 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. Actin filaments appeared to accumulate between mitochondria and INF2-enriched ER membranes at constriction sites. Thus, INF2-induced actin filaments may drive initial mitochondrial constriction, which allows Drp1-driven secondary constriction. Because INF2 mutations can lead to Charcot-Marie-Tooth disease, our results provide a potential cellular mechanism for this disease state.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/21096eb950bdff77308ad3924d69b681589bdc91
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In Molecular Biology
Citations in the corpus
- Mechanisms of mitochondrial fission and fusion. (2013, background): “This suggestion was nicely confirmed by the recent discovery that the ER protein INF-2 can promote mitochondrial fission by inducing constriction before Drp1 is recruited to mitochondria (Korobova et al. 2013).”
- Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “61,62 63 – 65 Mitophagy is a specialized form of autophagy, dedicated to the selective clearance of aged or damaged mitochondria.”
- Actin dynamics, architecture, and mechanics in cell motility. (2014, background): “Interestingly, another formin (INF2) localized at the endoplasmic reticulum of mammalian cells is reported to modulate mitochondria fission and mutations in INF2 can result in Charcot-Marie-Tooth neuropathy (157).”