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. 2017 May 2;36(12):1688–1706. doi: 10.15252/embj.201695916

Figure 8. Working model.

Figure 8

During embryonic retinal development, proliferating neuroblasts display an increase in mitochondrial number and rely on oxidative phosphorylation for ATP production, while recently differentiated retinal ganglion cells (RGCs) rely more on glycolysis and contain fewer mitochondria. The metabolic shift from the former profile to the latter is regulated by a hypoxia‐like response, which results in an increase in BNIP3L/NIX‐dependent mitophagy. This in turn decreases mitochondrial number, increases glycolysis and promotes RGC differentiation. Inhibition of autophagy (in Atg5‐deficient mice or following 3‐MA treatment), mitophagy (in NIX −/− retinas or following CsA treatment) or glycolysis (using the glycolysis inhibitor 2‐deoxyglucose (2DG) or the Pfkfb3 inhibitor 3PO) impairs neuronal differentiation (red boxes). Conversely, RGC differentiation is enhanced (green boxes) in response to deferoxamine mesylate (DFO)‐induced chemical hypoxia, mTOR inhibition with rapamycin, and after augmenting glycolysis with UK5099.