Open AccessRegulation of Mitochondrial Function and Cellular Energy Metabolism by Protein Kinase C‐λ/ι: A Novel Mode of Balancing Pluripotency
Author(s) -
Mahato Biraj,
Home Pratik,
Rajendran Ganeshkumar,
Paul Arindam,
Saha Biswarup,
Ganguly Avishek,
Ray Soma,
Roy Nairita,
Swerdlow Russell H.,
Paul Soumen
Publication year - 2014
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1817
Subject(s) - biology , microbiology and biotechnology , induced pluripotent stem cell , mitochondrion , embryonic stem cell , regulator , mitochondrial biogenesis , stem cell , anaerobic glycolysis , protein kinase c , glycolysis , kinase , biochemistry , metabolism , gene
A bstract 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 (PKCλ/ι), is a key regulator of mitochondrial function in ESCs. Depletion of PKCλ/ι in ESCs maintains their pluripotent state as evident from germline offsprings. Interestingly, loss of PKCλ/ι in ESCs leads to impairment in mitochondrial maturation, organization, and a metabolic shift toward glycolysis under differentiating condition. Our mechanistic analyses indicate that a PKCλ/ι‐hypoxia‐inducible factor 1α‐PGC1α axis regulates mitochondrial respiration and balances pluripotency in ESCs. We propose that PKCλ/ι could be a crucial regulator of mitochondrial function and energy metabolism in stem cells and other cellular contexts. S tem C ells 2014;32:2880–2892