OCIAD1 Controls Electron Transport Chain Complex I Activity to Regulate Energy Metabolism in Human Pluripotent Stem Cells.
Pluripotent stem cells (PSCs) derive energy predominantly from glycolysis and not the energy-efficient oxidative phosphorylation (OXPHOS). Differentiation is initiated with energy metabolic shift from glycolysis to OXPHOS. We investigated the role of mitochondrial energy metabolism in human PSCs using molecular, biochemical, genetic, and pharmacological approaches. We show that the carcinoma protein OCIAD1 interacts with and regulates mitochondrial complex I activity. Energy metabolic assays on live pluripotent cells showed that OCIAD1-depleted cells have increased OXPHOS and may be poised for differentiation. OCIAD1 maintains human embryonic stem cells, and its depletion by CRISPR/Cas9-mediated knockout leads to rapid and increased differentiation upon induction, whereas OCIAD1 overexpression has the opposite effect. Pharmacological alteration of complex I activity was able to rescue the defects of OCIAD1 modulation. Thus, hPSCs can exist in energy metabolic substates. OCIAD1 provides a target to screen for additional modulators of mitochondrial activity to promote transient multipotent precursor expansion or enhance differentiation.
['Shetty|Deeti K|DK|', 'Kalamkar|Kaustubh P|KP|', 'Inamdar|Maneesha S|MS|']
D015415:Biomarkers D002454:Cell Differentiation D004579:Electron Transport D042967:Electron Transport Complex I D004734:Energy Metabolism D005786:Gene Expression Regulation D006801:Humans D016130:Immunophenotyping D008648:Mesoderm D008928:Mitochondria D009363:Neoplasm Proteins D010085:Oxidative Phosphorylation D039904:Pluripotent Stem Cells
oxidative phosphorylation (OXPHOS) mitochondrial complex I transient multipotent precursor expansion early mesodermal progenitors (EMPs) energy metabolic sub-states of pluripotency human embryonic stem cells (hESCs) idebenone mitochondrial complex activity mitochondrial morphology in live cells ovarian carcinoma immunoreactive antigen domain containing-1 (OCIAD1)