Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis

Susan Chung, Petras P. Dzeja, Randolph S. Faustino, Andre Terzic

Research output: Chapter in Book/Report/Conference proceedingConference contribution

30 Scopus citations

Abstract

Differentiation of pluripotent low-energy requiring stem cells into the high-energy expenditure cardiac lineage requires coordination of genomic programming and energetic system maturation. Here, in a murine embryonic stem cell cardiac differentiation model, emergence of electrical and beating activity in cardiomyocytes developing within embryoid bodies was coupled with the establishment of the mitochondrial network and expansion of the creatine kinase (CK) phosphotransfer system. Stem cell cardiogenesis was characterized by increased total CK activity, an isoform shift manifested by amplified muscle CK-M mRNA levels and protein content, and the appearance of cardiac-specific CK-MB dimers. Treatment of differentiating stem cells with BMP2, a cardiogenic growth factor, promoted CK activity. CK-M clustered around developing myofibrils, sarcolemma, and the perinuclear compartment, whereas CK-B was tightly associated with myofibrillar α-actinin, forming wire-like structures extending from the nuclear compartment to the sarcolemma. Developmentally enhanced phosphotransfer enzyme-anchoring protein FHL2 coalesced the myofibrillar CK metabolic signaling circuit, providing an energetic continuum between mitochondria and the nascent contractile machinery. Thus, the evolving CK-catalyzed phosphotransfer network integrates mitochondrial energetics with cardiogenic programming, securing the emergence of energy-consuming cardiac functions in differentiating embryonic stem cells.

Original languageEnglish (US)
Title of host publicationMitochondria and Oxidative Stress in Neurodegenerative Disorders
PublisherBlackwell Publishing Inc.
Pages254-263
Number of pages10
ISBN (Print)9781573317139
DOIs
StatePublished - Dec 2008

Publication series

NameAnnals of the New York Academy of Sciences
Volume1147
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Differentiation
  • Embryonic stem cells
  • Energetic communication
  • Mitochondria
  • Phosphotransfer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

Fingerprint Dive into the research topics of 'Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis'. Together they form a unique fingerprint.

  • Cite this

    Chung, S., Dzeja, P. P., Faustino, R. S., & Terzic, A. (2008). Developmental restructuring of the creatine kinase system integrates mitochondrial energetics with stem cell cardiogenesis. In Mitochondria and Oxidative Stress in Neurodegenerative Disorders (pp. 254-263). (Annals of the New York Academy of Sciences; Vol. 1147). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1427.004