(150c) Novel Probe for in-Situ Monitoring of Mitochondrial DNA Methylation Reveals Unsynchronized Nucleus and Mitochondria Epigenome Dynamics

Mitochondria, as the center of energy production, plays an important role in cell homeostasis by regulating cellular metabolism and mediating cellular response to stress. Epigenetic changes such as DNA and histone methylation have been increasingly recognized to play a significant role in homeostasis and stress response. The cross-talking between metabolome and epigenome has attracted significant attention in recent years but with a major focus on how metabolism contributes to epigenomic changes. Few studies have been focused on how epigenetic modifications may alter mitochondria composition and activity. The study of epigenetic regulation on mitochondria function is vastly limited by lack of epigenetic monitoring tools either on in nucleus or in mitochondria and lack of knowledge in epigenetic regulatory role on mitochondrial DNA (mtDNA). To fill this gap, we designed a novel probe targeting methylated CpGs of mtDNA and demonstrated the capability of our probe to reveal spatial distribution of methylated mtDNA and capture mtDNA methylation change at single cell level. We were also able to track single-cell mtDNA and nDNA methylation simultaneously and discovered unsynchronized dynamics from nucleus and mitochondria. Our tool offers a unique opportunity to understand epigenetic regulation of mtDNA and its dynamic response to microenvironment and cellular changes.