Abstract
Mitochondrial division is important for mitochondrial distribution and function. Recent data have demonstrated that ER-mitochondria contacts mark mitochondrial division sites, but the molecular basis and functions of these contacts are not understood. Here we show that in yeast, the ER-mitochondria tethering complex, ERMES, and the highly conserved Miro GTPase, Gem1, are spatially and functionally linked to ER-associated mitochondrial division. Gem1 acts as a negative regulator of ER-mitochondria contacts, an activity required for the spatial resolution and distribution of newly generated mitochondrial tips following division. Previous data have demonstrated that ERMES localizes with a subset of actively replicating mitochondrial nucleoids. We show that mitochondrial division is spatially linked to nucleoids and that a majority of these nucleoids segregate prior to division, resulting in their distribution into newly generated tips in the mitochondrial network. Thus, we postulate that ER-associated division serves to link the distribution of mitochondria and mitochondrial nucleoids in cells. DOI:http://dx.doi.org/10.7554/eLife.00422.001.
Highlights
The distribution of mitochondria and mitochondrial DNA is accomplished through the engagement of multiple pathways, including mitochondrial division, fusion, motility, and tethering
The fraction of division events associated with ER-Mitochondria Encounter Structure (ERMES) foci (54–60%) is significantly higher than that predicted for a random association, based on the surface area of mitochondria associated with ERMES (Figure 1B and ‘Materials and methods’)
We show that ERMES and the Miro GTPase Gem1 function in the process of endoplasmic reticulum (ER)-associated Mitochondrial Division’ (ERMD), which serves to couple the segregation of mitochondria and mitochondrial DNA (mtDNA) in cells
Summary
The distribution of mitochondria and mitochondrial DNA (mtDNA) is accomplished through the engagement of multiple pathways, including mitochondrial division, fusion, motility, and tethering. Dnm and Drp form helices in vitro, whose diameters are significantly smaller than the diameter of unconstricted mitochondria (Ingerman et al, 2005; Bossy et al, 2010) This observation suggests that a mechanism for Dnm1/Drp1-independent constriction may exist to facilitate helix assembly as a first step toward mitochondrial division. We recently discovered that ER tubules wrap around mitochondria and mark a majority of mitochondrial division sites in yeast and mammalian cells (Friedman et al, 2011) These findings suggest that the process of ‘ER-associated Mitochondrial Division’ (ERMD) facilitates the creation of mitochondrial constriction sites, or geometric ‘hot spots’, for Dnm1/Drp helix assembly. The composition and biogenesis of ERMD sites are unknown
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