NIX-ing mitochondria: from development to pathology

Abstract

Hypoxia occurs physiologically in the developing body, and changing oxygen tensions are known to direct tissue differentiation; however, in the context of pathology, the same hypoxia‐activated mechanisms may negatively affect tissue function. In this issue of The EMBO Journal, Esteban‐Martínez et al (2017) report that programmed mitophagy, dependent on hypoxia‐induced NIP‐3‐like protein X (BNIP3L, best known as NIX), is an essential step in differentiation of both retinal neurons and inflammatory macrophages.

Figure 1. Hypoxia and mitophagy may direct cell differentiation in health and disease

Hypoxia‐induced mitophagy directs macrophage differentiation to pro‐inflammatory M1 cells and maturation of RGCs in the retina. In the brain, hypoxic conditions temporally correlate with the periods of increased synaptic pruning activity, which shapes brain circuitry in development, but if over‐activated in pathology, may eliminate viable synapses, thereby leading to brain function decline.