| Abstract |
Mitochondria are responsible for about 90% of ATP synthesis in most aerobic cells, which inevitably accompanies production of huge reactive oxygen species. Therefore, mitochondrial genome (mtDNA) is u...nder far more oxidative stress than nuclear genome. Resultantly, mtDNA as well as the organelle itself suffers higher damage over age. As mitochondria are a central hub for many cellular metabolisms including sugars, lipids, proteins, and nucleic acids in addition to energy production, the damage of mitochondria seriously affects the cellular overall processes leading to various common diseases. We have found Mitochondrial transcription factor A (TFAM) is a main component forming mtDNA higher structure, so called nucleoid. We also have shown TFAM is essential for its stability in mitochondrial matrix, in other words, protects mtDNA in vivo. Accordingly, overexpression of TFAM increases mtDNA and has beneficial effects for many pathologic situations such as heart failure, aging, neurodegenerative disease, diabetes, and so on. We found p32 protein among the TFAM-binding proteins. p32 is already reported by us to be in mitochondrial matrix and critical for oxidative phosphorylation. Through several p32 conditional knockout mice, we have shown p32 plays critical roles in efficient mitochondrial translation, regulation of IL6 production, antigen presentation, and differentiation to erythrocyte and B lymphocyte.show more
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113-2_p025