In the current study, we reported that under hypoxia and hypoglycemia, the combination of HIFα and TFE3 leads to a reduction in the utilization of promoter 1, while the increase in the selection of promoter 2, resulting in transcriptional dysregulation and an increase in the transcription of variant 4, followed by increase of SHMT2 isoform 3 under metabolic stress conditions. Here, TFE3 is linked to Hypoglycemia.