Table 3.
List of the cellular models used in MCM.
| Cell Type | Gene | Variants | Disease | Phenotype | Year | Ref. |
|---|---|---|---|---|---|---|
| Immortalized cells | MT-TL1 | m. 3243A > G | MELAS syndrome | defective protein synthesis, reduced activities of MRC. | 2011 | [41] |
| Immortalized cells | tRNALys | m. 8344A > G mutation | MERRF | increase ROS, oxidative stress, impaired mitochondrial bioenergetics. | 2017 | [42] |
| C2C12 | TAZ | TAZ-KO | BTHS | mitochondrial deficits, accumulation of MLCL, ROS, production increased, mitochondrial respiration decreased, myocyte differentiation impaired. | 2018 | [43] |
| Fibroblasts | tRNA(Leu/tRNA(Lys) | tRNA(Lys) | MELAS/MERRF | mitochondrial membrane potential and respiration rate decreased, incompetent mitochondria assembly, cell volume occupied by secondary lysosomes and residual bodies. | 1996 | [44] |
| Fibroblasts | TAZ | Positive-TAZ mutation | BTHS | cardiolipin, phosphatidylcholine, and phosphatidylethanolamine abnormalities in all tissues. | 2003 | [45] |
| iPSCs | KCNQ1 | R190Q | Long-QT Syndrome | susceptibility to catecholamine-induced tachyarrhythmia, beta-blockade attenuated duration of the action potential prolonged, reduction in I(Ks) current and altered channel activation and deactivation increased. | 2010 | [46] |
| iPSCs | mtDNA mutation | m. 3243A > G | MELAS | MELAS-iPSC-derived fibroblasts with high heteroplasmy levels showed defective CI activity, with low heteroplasmy levels showed normal CI activity. | 2015 | [47] |
| iPSCs | mtDNA mutation | m. 3243A > G | HMC | neuronal and cardiac maturation defects in iPSC line carrying a quite high proportion of m. 3243A > G, defective mitochondrial respiratory inhibits maturation of iPSC. | 2017 | [48] |
| iPSC-CMs | TAZ | c. 328T > C | MCM-BTHS | abnormal metabolic, structural and functional, assembled sparse and irregular sarcomeres. | 2014 | [49] |
| iPSC-CMs | HCM-mutation | MYH7/MYBPC3/TNNT2 | DD-HCM | impaired diastolic function, prolonged relaxation time, decreased relaxation rate and sarcomere length. | 2019 | [50] |
| iPSC-CMs | FXN | rs137854888 | FRDA- MCM | disorganized mitochondrial network and (mtDNA) depletion, α-actinin-positive cell sizes and BNP gene expression increased, intracellular iron accumulated, energy synthesis dynamics, ATP production rate impaired. | 2014 | [51] |
| iPSC-CMs | FXN | expanded GAA | FRDA | no biochemical phenotype, decreased membrane potential in neurons and progressive mitochondrial degeneration in cardiomyocytes, increased BNP expression and disrupted iron homeostasis. | 2013 | [52] |
| iPSC-CMs | MT-RNR2 A | m. 2336T > C | HCM | mitochondrial dysfunctions and ultrastructure defects, ATP/ADP ratio and membrane potential reduced, intracellular Ca2+ elevated, electrophysiological abnormalities. | 2018 | [53] |
| PBMC-iPSC | C1QBP | c. 823C > T | COXPD | iPSCs express pluripotent markers, have trilineage differentiation potential, carry C1QBP-L275F mutation, and have a normal karyotype. | 2014 | [54] |
| iPSC-CMs | DNAJC19 | rs137854888 | DCMA | highly fragmented and abnormally shaped mitochondria associated with imbalanced isoform ratio of OPA1. | 2020 | [55] |
Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; BNP, brain natriuretic peptide; BTHS, Barth syndrome; COXPD, combined oxidative phosphorylation deficiency; C1QBP, complement component 1 Q subcomponent-binding protein; DCMA, the dilated cardiomyopathy with ataxia syndrome; DD-HCM, diastolic dysfunction-hypertrophic cardiomyopathy; DNAJC19, mitochondrial import inner membrane translocase subunit TIM14; FXN, frataxin; HCM, hypertrophic cardiomyopathy; MELAS syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; MLCL, monolyso-cardiolipin; mtDNA, mitochondrial DNA; MT-TL1, mitochondrial mutant gene; OPA1, mitochondrial dynamin like GTPase; TAZ, gene tafazzin; tRNALys, transfer ribonucleic acid lysine.