Metabolic deregulation and aberrant epigenetic modifications are both separately known to be key corner stones of many chronic disease pathologies especially and including carcinogenesis. While an increasing number of studies suggest observed alterations to the epigenome may be directly associated with concurrently observed mitochondrial dysfunction, very little insight into the molecular mechanisms of these links is currently known. In an attempt to gain mechanistic insight to potential modes of mitochondrial-epigenetic regulation, we built a mitochondrial focused omics dataset within a controlled invitro system of glutamatergic neuronal differentiation from mouse embryonic stem cells. The strength of this model is the ability to track temporal changes as well as the previously well characterized metabolic shift from glycolysis to oxidative phosphorylation that is known to occur during stem cell differentiation. A robust data set of mitochondrial proteomics, whole genome ATAC-Seq, RNA-Seq, CHIP-Seq as well as mitochondrial targeted mass spectrometry has been acquired from the same cells as they passage through time. This multimodal approach has allowed for new insight into developing data driven hypothesis to assess direct mitochondrial-epigenetic axis of regulation which may be essential for neuronal differentiation. We anticipant these findings will provide new opportunities to explore previously overlooked mechanisms of regulation that may have implications in both development and disease.