Adenylate kinase AK2 isoform integral in embryo and adult heart homeostasis

Song Zhang, Satsuki Yamada, Sungjo Park, Aleksandr Klepinin, Tuuli Kaambre, Andre Terzic, Petras Dzeja

Research output: Contribution to journalArticlepeer-review

Abstract

Adenylate kinase2 (AK2) catalyzes trans-compartmental nucleotide exchange, but the functional implications of this mitochondrial intermembrane isoform is only partially understood. Here, transgenic AK2−/− null homozygosity was lethal early in embryo, indicating a mandatory role for intact AK2 in utero development. In the adult, conditional organ-specific ablation of AK2 precipitated abrupt heart failure with Krebs cycle and glycolytic metabolite buildup, suggesting a vital contribution to energy demanding cardiac performance. Depressed pump function recovered to pre-deletion levels overtime, suggestive of an adaptive response. Compensatory upregulation of phosphotransferase AK1, AK3, AK4 isozymes, creatine kinase isoforms, and hexokinase, along with remodeling of cell cycle/growth genes and mitochondrial ultrastructure supported organ rescue. Taken together, the requirement of AK2 in early embryonic stages, and the immediate collapse of heart performance in the AK2-deficient postnatal state underscore a primordial function of the AK2 isoform. Unsalvageable in embryo, loss of AK2 in the adult heart was recoverable, underscoring an AK2-integrated bioenergetics system with innate plasticity to maintain homeostasis on demand.

Original languageEnglish (US)
Pages (from-to)59-64
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume546
DOIs
StatePublished - Mar 26 2021

Keywords

  • Adaptation
  • Adenylate kinase
  • Homeostasis
  • Knockout
  • Metabolism
  • Phosphotransfer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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