TXNIP and Leigh syndrome: By using male TXNIP-KO mice, we here demonstrate evidence that TXNIP plays an important role in controlling the fasting-induced ER stress and activation of the UPR and autophagy in the liver in vivo and that TXNIP-KO mice develop LS because this controlling mechanism, especially the autophagy of damaged mitochondria, does not function well in the absence of TXNIP in the fasted state.