Fig. P1.

MECA-mediated mitochondria–cortex tethering. MECA comprises two interacting proteins, Num1 and Mdm36, and three organelles [i.e., mitochondria (mito), the ER, and the PM]. Num1 is a core component of MECA and possesses at least three regions of unique functionality: The CC domain mediates Num1 self-assembly in a manner regulated by Mdm36-dependent bridging/stabilizing interactions; the PH domain targets MECA to the cell cortex via interaction with PM-localized PI(4,5)P₂; and a region of Num1 outside the CC and PH domains interacts directly or indirectly via additional not-yet-identified MECA components (indicated by the black question mark) with the ER. Factors independent of Mdm36 and the CC region of Num1 contribute to Num1 self-assembly (indicated by the orange question mark) and the association of MECA with mitochondria (light blue oval).