Ping et al. demonstrate that mitochondria-to-plasma membrane anchoring is mediated by Num1 directly interacting with both organelles through two distinct and spatially separated lipid-specific binding domains. These findings suggest a general mechanism for interorganelle tethering.

Kraft and Lackner demonstrate that mitochondria drive the assembly of a tether, which serves to stably anchor the organelle itself as well as dynein to the plasma membrane. Thus, mitochondria–plasma membrane tethering influences when and where dynein is anchored, adding to the growing list of interorganelle contact site functions.

Organelle distribution is regulated over the course of the cell cycle to ensure that each of the cells produced at the completion of division inherits a full complement of organelles. In yeast, the protein Num1 functions in the positioning and inheritance of two essential organelles, mitochondria and the nucleus. Specifically, Num1 anchors mitochondria as well as dynein to the cell cortex, and this anchoring activity is required for proper mitochondrial distribution and dynein-mediated nuclear inheritance. The assembly of Num1 into clusters at the plasma membrane is critical for both of its anchoring functions. We have previously shown that mitochondria drive the assembly of Num1 clusters and that these mitochondria-assembled Num1 clusters serve as cortical attachment sites for dynein. Here we further examine the role for mitochondria in dynein anchoring. Using a GFP-αGFP nanobody targeting system, we synthetically clustered Num1 on eisosomes to bypass the requirement for mitochondria in Num1 cluster formation. Utilizing this system, we found that mitochondria positively impact the ability of synthetically clustered Num1 to anchor dynein and support dynein function even when mitochondria are no longer required for cluster formation. Thus, the role of mitochondria in regulating dynein function extends beyond simply concentrating Num1; mitochondria likely promote an arrangement of Num1 within a cluster that is competent for dynein anchoring. This functional dependency between mitochondrial and nuclear positioning pathways likely serves as a mechanism to order and integrate major cellular organization systems over the course of the cell cycle.

The shape and position of mitochondria are intimately connected to both mitochondrial and cellular function. Mitochondrial anchors play a central role in mitochondrial positioning by exerting spatial, temporal, and contextual control over the cellular position of the organelle. Investigations into the molecular mechanisms of mitochondrial anchoring are still in the early stages, and we are beginning to appreciate the number and variety of anchors that exist. From the insight gained thus far, it is clear that mitochondrial anchoring has functional and physiological consequences that extend beyond mitochondrial positioning to other critical cellular processes.

Mitochondrial anchors have functions that extend beyond simply positioning mitochondria. In budding yeast, mitochondria drive the assembly of the mitochondrial anchor protein Num1 into clusters, which serve to anchor mitochondria as well as dynein to the cell cortex. Here, we explore a conserved role for mitochondria in dynein anchoring by examining the tethering functions of the evolutionarily distant Schizosaccharomyces pombe Num1 homologue. In addition to its function in dynein anchoring, we find that S. pombe Num1, also known as Mcp5, interacts with and tethers mitochondria to the plasma membrane in S. pombe and Saccharomyces cerevisiae. Thus, the mitochondria and plasma membrane-binding domains of the Num1 homologues, as well as the membrane features these domains recognize, are conserved. In S. pombe, we find that mitochondria impact the assembly and cellular distribution of Num1 clusters and that Num1 clusters actively engaged in mitochondrial tethering serve as cortical attachment sites for dynein. Thus, mitochondria play a critical and conserved role in the formation and distribution of dynein-anchoring sites at the cell cortex and, as a consequence, impact dynein function. These findings shed light on an ancient mechanism of mitochondria-dependent dynein anchoring that is conserved over more than 450 million years of evolution, raising the intriguing possibility that the role mitochondria play in dynein anchoring and function extends beyond yeast to higher eukaryotes.