Pluripotent stem cells and mitochondrial dysfunction

Abstract

Embryonic stem cells (ESCs) are derived from the inner-cell-mass (ICM) of blastocysts. ESC and induced pluripotent stem cell (iPSC) lines are immortal, meaning that they have unlimited proliferation potential. They are also pluripotent; that is, they can differentiate into lineages derived from all 3 major germ layers of the embryo. Consequently, these cells have been widely investigated in the development of regenerative medicine therapies. Human ESCs have been regarded as important research tools for the investigation into early development of the human embryo.Mitochondria are the powerhouses capable of providing the majority of energy within the cell and performing important metabolic functions such as the Krebs cycle. The well-known endosymbiotic theory [1] has suggested that the mitochondrion was originally derived from a prokaryotic cell that invaded a larger, nucleated host cell. Mitochondria indeed contain their own mitochondrial DNA (mtDNA) in a circular form, similar to the bacterial genome. Mitochondrial genomes encode several essential genes of the eukaryotic respiratory machinery. However, most of the components of the respiratory machinery and factors controlling mitochondrial biogenesis are encoded in the nucleus. The cooperation and communication between mitochondria and nuclei are conducted by retrograde signals, such as energy supply and redox signaling and this currently poorly-understood communication is essential for balancing energy production and demand in the cell. Targeting mitochondria metabolism for inherited disease by using pluripotent stem cells is still a major therapeutic direction for cell therapy.