Figure 2.

(2-1) Mitochondria move along the microtubules in response to changes in the local Ca²⁺ and ATP, in other words, buffering and metabolic demand. Mitochondria with normal membrane potential perform anterograde movement (move towards the periphery), whereas loss of membrane potential results in increased retrograde transport towards the cell body. The cargo adaptor proteins, mitochondrial Rho (Miro) GTPases and Milton, link mitochondria to microtubules via kinesin heavy chain (KHC). Miro binds Milton in a Ca²⁺-unbound state, and thus mitochondria become attached to microtubules. When Miro binds Ca²⁺, it is dislodged from Milton and mitochondria are uncoupled from microtubules. Moreover, Miro1 and Miro2 are required for normal mitochondrial cristae architecture, ER–mitochondria contact sites, and a normal Ca²⁺ uptake. (2-2) Absence of Miro results in decreased ER–mitochondria contacts, as a consequence of which ER/mitochondrial handling of Ca²⁺ is severely affected, and there is a significantly larger loss of Ca²⁺ from ER stores.