Regulation of mitochondrial function and cellular energy metabolism by protein kinase C-?/?: a novel mode of balancing pluripotency.

ABSTRACT: Pluripotent stem cells (PSCs) contain functionally immature mitochondria and rely upon high rates of glycolysis for their energy requirements. Thus, altered mitochondrial function and promotion of aerobic glycolysis are key to maintain and induce pluripotency. However, signaling mechanisms that regulate mitochondrial function and reprogram metabolic preferences in self-renewing versus differentiated PSC populations are poorly understood. Here, using murine embryonic stem cells (ESCs) as a model system, we demonstrate that atypical protein kinase C isoform, PKC lambda/iota (PKC?/?), is a key regulator of mitochondrial function in ESCs. Depletion of PKC?/? in ESCs maintains their pluripotent state as evident from germline offsprings. Interestingly, loss of PKC?/? in ESCs leads to impairment in mitochondrial maturation, organization, and a metabolic shift toward glycolysis under differentiating condition. Our mechanistic analyses indicate that a PKC?/?-hypoxia-inducible factor 1?-PGC1? axis regulates mitochondrial respiration and balances pluripotency in ESCs. We propose that PKC?/? could be a crucial regulator of mitochondrial function and energy metabolism in stem cells and other cellular contexts.

SUBMITTER: Mahato B 

PROVIDER: S-EPMC4198455 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature