Autophagy-lysosomal related protein, TFEB, may serve as a biomarker of mechanical asphyxia: A primary study

The postmortem diagnosis of death from mechanical asphyxia (DMA) remains challenging owing to the absence of specific morphological signs. The present study evaluated the potential of transcription factor EB (TFEB), a master regulator of the autophagy-lysosomal pathway (ALP), as a biomarker for MA. Through transcriptomic analysis, molecular docking, molecular dynamics (MD) simulations, and an SH-SY5Y cell hypoxia model, we observed that TFEB expression was upregulated and nuclear translocation was induced during the initial phase of hypoxia. Following prolonged hypoxia (24 h), however, autophagy flux arrest and lysosomal dysfunction were observed. Mechanistically, we found that tomatidine (TA) could ameliorate these dysfunctions by activating the AMPK-TFEB signalling axis. In human brain tissue samples collected during the early postmortem interval (PMI), the MA group exhibited significantly increased TFEB and LC3 expression and decreased LAMP1 expression. ROC curve analysis demonstrated high diagnostic accuracy of TFEB for MA (AUC = 0.8526). Collectively, these findings identify TFEB and ALP-associated proteins as potential molecular markers for the postmortem diagnosis of MA.