Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer

Petras P Dzeja, Ryan Bortolon, Carmen M Terzic, Ekshon L. Holmuhamedov, Andre Terzic

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Exchange of information between the nucleus and cytosol depends on the metabolic state of the cell, yet the energy-supply pathways to the nuclear compartment are unknown. Here, the energetics of nucleocytoplasmic communication was determined by imaging import of a constitutive nuclear protein histone H1. Translocation of H1 through nuclear pores in cardiac cells relied on ATP supplied by mitochondrial oxidative phosphorylation, but not by glycolysis. Although mitochondria clustered around the nucleus, reducing the distance for energy transfer, simple nucleotide diffusion was insufficient to meet the energetic demands of nuclear transport. Rather, the integrated phosphotransfer network was required for delivery of high-energy phosphoryls from mitochondria to the nucleus. In neonatal cardiomyocytes with low creatine kinase activity, inhibition of adenylate kinase-catalyzed phosphotransfer abolished nuclear import. With deficient adenylate kinase, nucleoside diphosphate kinase, which secures phosphoryl exchange between ATP and GTP, was unable to sustain nuclear import. Up-regulation of creatine kinase phosphotransfer, to mimic metabolic conditions of adult cardiac cells, rescued H1 import, suggesting a developmental plasticity of the cellular energetic system. Thus, mitochondrial oxidative phosphorylation coupled with phosphotransfer relays provides an efficient energetic unit in support of nuclear transport.

Original languageEnglish (US)
Pages (from-to)10156-10161
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number15
DOIs
StatePublished - Jul 23 2002

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Cell Nucleus Active Transport
Mitochondria
Adenylate Kinase
Oxidative Phosphorylation
Creatine Kinase
Adenosine Triphosphate
Nucleoside-Diphosphate Kinase
Nuclear Pore
Energy Transfer
Glycolysis
Nuclear Proteins
Guanosine Triphosphate
Cardiac Myocytes
Cytosol
Histones
Up-Regulation
Nucleotides

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Energetic communication between mitochondria and nucleus directed by catalyzed phosphotransfer. / Dzeja, Petras P; Bortolon, Ryan; Terzic, Carmen M; Holmuhamedov, Ekshon L.; Terzic, Andre.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 15, 23.07.2002, p. 10156-10161.

Research output: Contribution to journalArticle

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