| First Author | Zhang S | Year | 2021 |
| Journal | Biochem Biophys Res Commun | Volume | 546 |
| Pages | 59-64 | PubMed ID | 33571905 |
| Mgi Jnum | J:305579 | Mgi Id | MGI:6706032 |
| Doi | 10.1016/j.bbrc.2021.01.097 | Citation | Zhang S, et al. (2021) Adenylate kinase AK2 isoform integral in embryo and adult heart homeostasis. Biochem Biophys Res Commun 546:59-64 |
| abstractText | 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. |
