Molecular models of mitochondrial motility and tethering. (a) In yeast, mitochondria are actively transported to the growing bud via Myo2-driven transport along the actin cytoskeleton. Myo2-driven transport requires either Mmr1 or Ypt11 [76–82]. Mother- and bud-specific mitochondrial tethers ensure that both cells retain part of the essential mitochondrial compartment. The mother specific tether MECA (mitochondria-ER-cortex anchor) is composed of three membranes, the plasma membrane (PM), ER and mitochondria, and at least two proteins, Num1 and Mdm36 . In addition to serving as a mitochondrial adaptor for Myo2, Mmr1 functions to tether mitochondria to ER sheets at the bud tip . (b) A model for activity-dependent transport and tethering of mitochondria in axons. The conserved MOM Rho-like GTPase Miro and its binding partner Milton function as a mitochondrial receptor for kinesin. In active synaptic regions, Ca2+-binding by Miro triggers a confirmation change that disrupts kinesin-driven mitochondrial transport [98, 99]. Ca2+-mediated confirmation changes have been proposed to disrupt the interaction between Miro/Milton with kinesin (shown here) or kinesin with microtubules. In response to neuronal activity (elevated Ca2+), syntaphilin is also recruited to mitochondria and functions as a static mitochondria-microtubule tether .