Mitochondria undergo constant quality control, in which, among others, mitophagy and the mitochondrial unfolded protein response (mtUPR) play a major role. Īn increase in the mitochondrial content of cells is termed mitochondrial biogenesis. The disruption of nutrient sensing and mitonuclear proteostasis plays a pathogenic role in metabolic and neoplastic diseases. Therefore, the transcriptional programs can accommodate the actual nutrient and energy charge of cells. This web of transcription factors responds to changes in nutrient levels (amino acids, oxygen, NAD +, etc.) and cellular energy charge. The appropriate flux of protein from the cytosol to the mitochondria requires the coordinated regulation of nuclear transcription by a large set of nuclear transcription factors. There is a dominant flow of information and material from the nucleus and the cytosol to the mitochondria, termed anterograde signaling. Most mitochondrial genes are coded in the nucleus. Optimal mitochondrial biogenesis requires the coordinated expression of nuclear and mitochondrial genes.
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