UCP2 Regulates Energy Metabolism and Differentiation Potential of Human Pluripotent Stem Cells

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2011 Nov 17

PMID 22085932

Citations 266

Authors

Jin Zhang

Ivan Khvorostov

Jason S Hong

Yavuz Oktay

Laurent Vergnes

Esther Nuebel

Paulin N Wahjudi

Kiyoko Setoguchi

Geng Wang

Anna Do

Hea-Jin Jung

J Michael McCaffery

Irwin J Kurland

Karen Reue

Wai-Nang P Lee

Carla M Koehler

Michael A Teitell

Affiliations

Soon will be listed here.

Abstract

It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O(2) at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F(1)F(0) ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential.

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