A conserved mechanism for mitochondrial anchoring and integrated organelle positioning
Lauren M. Kraft1, Laura L. Lackner1 1Northwestern University
Inter-organelle contacts facilitate communication between organelles and impact fundamental cellular functions. In S. cerevisiae, also known as budding yeast, the mitochondria-ER-cortex anchor (MECA) tethers mitochondria to the ER and plasma membrane. We find the assembly of Num1, the core component of MECA, requires mitochondria. Once assembled, Num1 clusters persistently anchor mitochondria to the cell cortex. Num1 clusters also function to anchor dynein to the plasma membrane, where dynein captures and walks along astral microtubules to help orient the mitotic spindle. We find that dynein is anchored by Num1 clusters that have been assembled by mitochondria. When mitochondrial inheritance is inhibited, Num1 clusters are not assembled in the bud and defects in dynein-mediated spindle positioning are observed. The mitochondrial-dependent assembly of a dual-function cortical anchor provides a mechanism to integrate the positioning and inheritance of two essential organelles and expands the function of organelle contact sites. To further investigate conserved features of mitochondrial tethering mechanisms and the integration of organelle positioning pathways, we turned to the Num1 homolog in S. pombe. Like S. cerevisiae Num1, S. pombe Num1 localizes to the cell cortex through a pleckstrin homology domain that exhibits specificity for PI(4,5)P2. Our data indicate that S. pombe Num1 also interacts with mitochondria and that the interaction is mediated by a coiled-coil domain that is conserved between the Num1 homologs. We find that S. pombe Num1 forms clusters that tether mitochondria to the cell cortex and that the formation of these clusters likely depends on an interaction with mitochondria. When expressed in S. cerevisiae, S. pombe Num1 can tether mitochondria to the cell cortex indicating that the conserved membrane binding domains shared between the Num1 homologs recognize conserved features on each membrane. In addition, our data suggest that, similar to S. cerevisiae, the Num1-mitochondria interaction influences Num1-dependent dynein anchoring in S. pombe. These data suggest a mechanism of membrane contact site assembly and integrated organelle positioning that is conserved over 350 million years of evolution.
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