Mitochondria and Hypoxia: Metabolic Crosstalk in Cell-Fate Decisions

Publication date: Available online 28 February 2018
Source:Trends in Endocrinology & Metabolism
Author(s): David Bargiela, Stephen P. Burr, Patrick F. Chinnery
Alterations in mitochondrial metabolism influence cell differentiation and growth. This process is regulated by the activity of 2-oxoglutarate (2OG)-dependent dioxygenases (2OGDDs) – a diverse superfamily of oxygen-consuming enzymes – through modulation of the epigenetic landscape and transcriptional responses. Recent reports have described the role of mitochondrial metabolites in directing 2OGDD-driven cell-fate switches in stem cells (SCs), immune cells, and cancer cells. An understanding of the metabolic mechanisms underlying 2OGDD autoregulation is required for therapeutic targeting of this system. We propose a model dependent on oxygen and metabolite availability and discuss how this integrates 2OGDD metabolic signalling, the hypoxic transcriptional response, and fate-determining epigenetic changes.



http://ift.tt/2HUrpib