OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

Andreas D Hofmann,Manja Wobus,Martin Bornhäuser,Mandy Beyer,Gerhard Rödel,Udo Krause-Buchholz,Wolfgang Wagner

doi:10.1371/journal.pone.0035160

Andreas D Hofmann, Manja Wobus + Show 5 more

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https://doi.org/10.1371/journal.pone.0035160

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Journal: PLoS ONE	Publication Date: Apr 16, 2012
Citations: 112	License type: CC BY 4.0

Affiliation: University Hospital Carl Gustav Carus, TU Dresden

Abstract

Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation.

Highlights

Mitochondria are the site of the oxidative phosphorylation system (OXPHOS) that comprises four enzyme complexes of the respiratory chain (RC), two mobile electron carriers as well as the ATP synthase
Ubiquinone and cytochrome c are mediating the further transport of electrons to complex III (CIII) and complex IV (CIV)
During the redox reactions at CI, CIII and CIV protons are transferred through the inner mitochondrial membrane leading to an electrochemical gradient that is utilized by the ATP synthase (CV; complex V) to produce ATP

Summary

Introduction

Mitochondria are the site of the oxidative phosphorylation system (OXPHOS) that comprises four enzyme complexes of the respiratory chain (RC), two mobile electron carriers (ubiquinone, cytochrome c) as well as the ATP synthase. Ubiquinone and cytochrome c are mediating the further transport of electrons to complex III (CIII) and complex IV (CIV). The protein complexes of the OXPHOS system are encoded by two genomes requiring a coordinated synthesis and assembly into functional entities to establish an active RC. Beside their well-known function in energy supply, mitochondria play pivotal roles in other essential cellular processes, such as the formation of Fe-S-clusters, calcium homeostasis, oxygen sensing, cellular proliferation, apoptosis and aging [1]. The peroxisome proliferatoractivated receptor gamma coactivator 1-alpha (PGC-1a) that acts as a transcriptional coactivator, was identified as the key regulator of mt biogenesis [6]

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