Mitochondria participate in various metabolic pathways, and their dysregulation results in multiple disorders, including aging-related diseases. However, the metabolic changes and mechanisms of
mitochondrial disorders are not fully understood. Here, we found that induced pluripotent stem cells (iPSCs) from a patient with
mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (
MELAS) showed attenuated proliferation and survival when glycolysis was inhibited. These deficits were rescued by
taurine administration. Metabolomic analyses showed that the ratio of the reduced (GSH) to
oxidized glutathione (
GSSG) was decreased; whereas the levels of
cysteine, a substrate of GSH, and oxidative stress markers were upregulated in
MELAS iPSCs.
Taurine normalized these changes, suggesting that
MELAS iPSCs were affected by the oxidative stress and
taurine reduced its influence. We also analyzed the retinal pigment epithelium (RPE) differentiated from
MELAS iPSCs by using a three-dimensional culture system and found that it showed epithelial mesenchymal transition (EMT), which was suppressed by
taurine. Therefore,
mitochondrial dysfunction caused metabolic changes, accumulation of oxidative stress that depleted GSH, and EMT in the RPE that could be involved in
retinal pathogenesis. Because all these phenomena were sensitive to
taurine treatment, we conclude that administration of
taurine may be a potential new therapeutic approach for mitochondria-related
retinal diseases.