Table 1.
Phenotypes of associated diseases and expression changes in each AK isozyme.
| Isozyme | Intracellular Localization/ Highly Expressed Tissues |
Physiological Characteristics | Related Human Diseases | Animal Model/Cultured Cell |
|---|---|---|---|---|
| AK1 | Cytosol/nuscle, brain, heart, testis | Highly expressed in skeletal muscles, brain, and erythrocytes [1] | Non-obstructive azoospermia [30] Hematological abnormality [20,21,22] |
KO mouse, inhibited sperm motility under specific conditions [30,33,99] Tg medaka, increased spontaneous locomotor activity [32] and reduced tolerance to ischemic stress [35] |
| AK2 | Mitochondrial intermembrane space/liver, kidney, heart |
Supply of ADP to the adenine nucleotide transporter [100] Regulation of mitochondrial apoptosis [39] Transfer of energy from the mitochondria [36] |
Reticular dysgenesis [40,41,42,47] | KO drosophila, lethal at the larval stage [1] KO zebrafish, reticular dysgenesis, and affected sensory hair cells [48] KO mouse, lethal in the early embryo [46] |
| AK3 | Mitochondrial matrix/all tissues except for red blood cell |
Mitochondrial energy metabolism [1] Low expression in pancreatic beta cells [60] |
Not reported | HeLa cell, slow growth [61] |
| AK4 | Mitochondrial matrix/kidney, liver, brain, heart, stomach, intestine, gonads |
Mitochondrial energy metabolism [6,67] Hypoxia-related mitochondrial regulation [67,69,70] |
Not reported | Smooth muscle cells, AK4 KD enhanced mitochondrial respiration and decreased glycolytic metabolism [68] Hela cell, AK4 KD decreased mitochondrial activity [70] |
| AK5 | Cytosol nucleus/highly expressed in brain | Energy regulation in brain [76] | Non-paraneoplastic limbic encephalitis [77] | AZ521 and MKN74 cells, AK5 KD inhibited growth and autophagy and increased apoptosis [80] |
| AK6 | Nucleus/all tissues | Nuclear energy metabolism [81] | Not reported | C. elegans, growth inhibition [82,83] |
| AK7 | Cytosol/lung, trachea, testis, mammary gland tissue | Expressed in ciliated tissues and testes [3] | Respiratory primary ciliary dyskinesia [91] Morphological anomalies of the flagella [92] Multiple morphological anomalies of the flagella, Oligoasthenoteratozoospermia [93] |
KO mouse, primary ciliary dyskinesia hydrocephalus, abnormal spermatogenesis, mucus accumulation in the sinuses, and impaired spermatogenesis [3] |
| AK8 | Cytosol/liver, paancreas, lung, testis | Associated with the axoneme [95] | Not reported | KO mouse, hydrocephalus [96] |
| AK9 | Cytosol, nucleus/ highly expressed in pituitary gland, trachea, thymus, testis, mammary gland | Highly expressed in the pituitary gland, trachea, thymus, and testis [97] | Congenital myasthenic syndrome [98] | Not reported |
KO: knockout, KD: knockdown, Tg: transgenic.