Figure 2.

The reciprocal regulation of the mitochondrial dynamics machinery by the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. The activated MAPK pathway promotes mitochondrial fission by activating Drp1 as well as inhibiting Mfn1 activity. Conversely, Mfn1 has been shown to interact with Ras while Mfn2 has been shown to interact with either Ras or Raf; these interactions have been shown to inhibit MAPK activity and some of its physiological consequences. Activated Akt can directly phosphorylate and activate Drp1 and promote mitochondrial fission. Additionally, Mfn2 can interact with the mammalian target of rapamycin complex 2 (mTORC2) complex, via interactions with rapamycin-insensitive companion of mTOR (RICTOR), which inhibits PI3K/Akt activity.