Mitochondria are energy producing organelles that consume oxygen and substrates to generate the vast majority of ATP while producing reactive oxygen species in the process. They also participate in a wide range of other cellular processes, including cellular metabolism, signal transduction, oxidative stress, apoptosis and ageing-associated pathologies. They are highly dynamic organelles that are continuously turnover through biogenesis, fission, fusion, and autophagy. Mitochondria undergo biogenesis to meet energy demands and turnover to ensure cellular quality by remove compromised organelles. In our previous studies unraveled the effects of nutrients supplement on mitochondrial biogenesis. This experimental plan will propose to further understand the nutrients how to modulate the damaged mitochondria biogenesis and turnover. Three specific aims of this plan are listed: 1. Estimation of biogenesis and turnover in compromised mitochondrion. 2. Determination of modulating mechanism of biogenesis and turnover in damaged mitochondrion. 3. Evaluation of nutrients supplementation how to modulate mitochondrial biogenesis and turnover through cellular and animal models. This plan include two cell models, cell lines and primary cells from ex vivo study, and one real-time bioluminescence tracking in vivo animal model to evaluate the proposals. Importantly, our fusion cellular model is a novel evaluation system to estimate the particular mitochondria turnover, and in animal model will provide real-time tracking concept and long-term monitoring to follow the fates of nutrients intervention. In this study, we plan to characterize the fates of damaged mitochondria in cells, modulation of nutrients on mitochondrial biogenesis and turnover, and create a novel system to evaluate mitochondria turnover. This knowledge could bring new ways to better understand mitochondrial defect in metabolic-related diseases and aging process and also provide possible preventive and therapeutic strategy.
|Effective start/end date||8/1/14 → 7/31/15|
- mitochondrial DNA
- mitochondrial biogenesis
- mitochondrial turnover