Role of Nix in the Maturation of Erythroid Cells through Mitochondrial Autophagy

Selective mitochondrial clearance by autophagy is crucial for maintaining proper cellular function and cellular homeostasis. Reticulocytes, which completely remove their mitochondria during terminal maturation, provide a good physiological model to study the mechanisms of such clearance. Nip-like protein X (Nix, also known as Bnip3L), an atypical BH3-only member of the Bcl-2 family, plays an essential role in mitochondrial autophagy occurring during erythroid maturation. Nix^-/- reticulocytes show an abnormal retention of mitochondria and a defect in the sequestration of mitochondria by autophagosomes. Nix is not required for autophagosome formation; instead, its role in mitochondrial clearance during erythroid maturation likely involves both dissipation of mitochondrial membrane potential (δψm) and interaction with autophagosomes. Given that mitochondria are important organelles for energy production and regulation of cell death, elucidating the mechanisms underlying selective mitochondrial autophagy not only will help us to understand the mechanisms for erythroid maturation, but also may provide insights into mitochondrial quality control by autophagy in protection against aging, cancer, and neurodegenerative diseases.