Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging

摘要: Heme, a major functional form of iron in the cell, is synthesized mitochondria by ferrochelatase inserting ferrous into protoporphyrin IX. Heme deficiency was induced with N-methylprotoporphyrin IX, selective inhibitor ferrochelatase, two human brain cell lines, SHSY5Y (neuroblastoma) and U373 (astrocytoma), as well rat primary hippocampal neurons. cells decreases mitochondrial complex IV, activates nitric oxide synthase, alters amyloid precursor protein, corrupts zinc homeostasis. The metabolic consequences resulting from heme seem similar to dysfunctional neurons patients Alzheimer's disease. Heme-deficient or die when differentiate proliferate, respectively. role these observations could result its interaction regulatory motifs specific proteins secondary compromised mitochondria. Common causes include aging, vitamin B6, exposure toxic metals such aluminum. Iron B6 deficiencies are especially important because they widespread, but also preventable supplementation. Thus, dysregulation may be an component neurodegenerative process.