Figure 3. ER-mitochondria contacts are important for mitochondrial dynamics.

a | Confocal microscopy images showing the mitochondrial division machinery proteins DRP1 (dynamin-related protein 1) and MFF (mitochondrial fission factor) in Cos-7 cells and the yeast division machinery dynamin Dnm1 localizing to positions where endoplasmic reticulum (ER) tubules circumscribe the mitochondrial membrane. b,c | Live confocal fluorescence time-lapse images of Cos-7 cells (b) and yeast cells (c) showing mitochondrial constriction followed by division taking place at the site of an ER tubule crossing the mitochondria. Arrows indicate the initial site of constriction and arrowheads indicate the site of mitochondrial division, d | The Ca²⁺ binding protein MIRO (mitochondrial Rho GTPase), which regulates mitochondrial motility, localizes to a position (indicated by an arrow) where an ER tubule crosses over the mitochondrial membrane in a Cos-7 cell, e | A model of multiple factors that converge at ER–mitochondria contact sites to regulate mitochondrial dynamics. Both mitochondria and the ER are linked to microtubules by factors that associate with the microtubule motor kinesin 1. In the case of mitochondria, this occurs through kinesin 1 binding to the cytoplasmic protein MILTON, which in turn binds MIRO on the outer mitochondrial membrane. MIRO is important for mitochondrial movement. Less is known about the ER proteins that tether the ER to microtubules. Mitochondrial constriction mediated by DRP1 occurs at sites of ER–mitochondria contact, and one possibility is that ER contact promotes initial constriction of the mitochondria before DRP1 recruitment. Ultimately, mitochondrial fission is promoted by DRP1 and its cofactor MFF. f | Volume rendering of structured illumination microscopy images show a yeast cell during coordinated organelle inheritance into the bud. This is mediated by contact sites between the ER and the mitochondria, and normal ER inheritance is important for mitochondrial inheritance. Mitochondrial MYO2 receptor-related protein 1 (Mmr1) links the mitochondria to the ER during inheritance and accumulates between the mitochondria (shown in red) and the cortical ER (labelled by green fluorescent protein (GFP)–Sec63, in green). The bud tip is indicated by an asterisk. Scale bars represent 1 μM. Images in a–c are reproduced, with permission, from REF. 4 © (2011) American Association for the Advancement of Science. The image in d is reproduced, with permission, from REF. 12 © (2011) National Academy of Sciences. Images in f are reproduced, with permission, from REF. 48 © (2011) Elsevier. BFP, blue fluorescent protein; CFP, cyan fluorescent protein; HDEL, His-Asp-Glu-Leu; KDEL, Lys-Asp-Glu-Leu.