Nix (gene)

Nix is a pro-apoptotic gene that is regulated by Histotoxic hypoxia. It expresses a signaling protein related to the BH3-only family. This protein induces autophagy, an intracellular function by which cytoplasmic components are delivered to the lysosome to be broken down and used elsewhere or excreted from the cell.[1] This protein is important in development because it allows cells to have a consistent store of cellular components.[2] It also holds an important role in the differentiation and maturation of erythrocytes and lymphocytes by the process of mitophagy with the help of its regulator BNIP3.[3] Using a gene knockout technique in mice, scientists have been able to attribute this pruning of mitochondria and induction of cellular necrosis to the expression of the Nix gene.[1] The Nix protein may be associated with certain kinds of cancer formation. In mouse models, loss of Nix resulted in a delayed onset of tumors for pancreatic cancer, and was additionally associated with reduced mitophagy and increased oxidative metabolism. Nix therefore may be a tumor promoter for pancreatic cancer.[4]

Not only does it hold a role in the differentiation of these immune and oxygen-carrying cells, but it also affects the development and maintenance of heart tissue. It has been found to be a cause of pathologic hypertrophy and cardiomyocyte apoptosis involved in congenital heart disease.[5] The effects of Nix are amplified in the neonatal heart compared to the adult heart. Overexpression of Nix in the fetal mouse has been found to cause severe growth retardation and massive cardiomyocyte apoptosis often followed by lethality. These early interactions between the fetal heart and Nix expression are thought to have a role in the development of adult heart disease.[3]

References

  1. ^ a b Zhang J, Ney PA (July 2009). "Role of BNIP3 and NIX in cell death, autophagy, and mitophagy". Cell Death and Differentiation. 16 (7): 939–46. doi:10.1038/cdd.2009.16. PMC 2768230. PMID 19229244.
  2. ^ Mizushima N, Levine B (September 2010). "Autophagy in mammalian development and differentiation". Nature Cell Biology. 12 (9): 823–30. doi:10.1038/ncb0910-823. PMC 3127249. PMID 20811354.
  3. ^ a b Dorn GW (August 2010). "Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors". Journal of Cardiovascular Translational Research. 3 (4): 374–83. doi:10.1007/s12265-010-9174-x. PMC 2900478. PMID 20559783.
  4. ^ MacLeod, Kay F. (2020). "Mitophagy and Mitochondrial Dysfunction in Cancer". Annual Review of Cancer Biology. 4: 41–60. doi:10.1146/annurev-cancerbio-030419-033405.
  5. ^ Dorn GW (July 2005). "Physiologic growth and pathologic genes in cardiac development and cardiomyopathy". Trends in Cardiovascular Medicine. 15 (5): 185–9. doi:10.1016/j.tcm.2005.05.009. PMID 16165015.

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