Succinate as a New Actor in Pluripotency and Early Development?

Abstract

Pluripotent cells have been stabilized from pre- and post-implantation blastocysts, representing respectively naïve and primed stages of embryonic stem cells (ESCs) with distinct epigenetic, metabolic and transcriptomic features. Beside these two well characterized pluripotent stages, several intermediate states have been reported, as well as a small subpopulation of cells that have reacquired features of the 2C-embryo (2C-like cells) in naïve mouse ESC culture. Altogether, these represent a continuum of distinct pluripotency stages, characterized by metabolic transitions, for which we propose a new role for a long-known metabolite: succinate. Mostly seen as the metabolite of the TCA, succinate is also at the crossroad of several mitochondrial biochemical pathways. Its role also extends far beyond the mitochondrion, as it can be secreted, modify proteins by lysine succinylation and inhibit the activity of alpha-ketoglutarate-dependent dioxygenases, such as prolyl hydroxylase (PHDs) or histone and DNA demethylases. When released in the extracellular compartment, succinate can trigger several key transduction pathways after binding to SUCNR1, a G-Protein Coupled Receptor. In this review, we highlight the different intra- and extracellular roles that succinate might play in the fields of early pluripotency and embryo development.

Chemical Imaging Reveals Diverse Functions of Tricarboxylic Acid Metabolites in Root Growth and Development

“…TCA metabolites are increasingly being studied for their roles in signaling in a range of different organisms [19][20][21][22] . However, analyzing TCA metabolite signaling has been highly challenging because most biosynthetic genes are essential and cannot be inhibited or knocked out without causing severe pleiotropic effects or lethality.…”

“…Full fragmentation spectra are provided in the Supplementary Information (Supplementary Information Figs. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”