In this section
@article{Prak:2026:10.1038/s41419-025-08187-7,
author = {Prak, K and Luft, C and Tsefou, E and Chavez-Olortegui, C and Kriston-Vizi, J and Ketteler, R and Braga, V},
doi = {10.1038/s41419-025-08187-7},
journal = {Cell Death and Disease},
title = {Functional analyses and integrated mechanisms of cellular destruction by L-amino acid oxidase},
url = {http://dx.doi.org/10.1038/s41419-025-08187-7},
volume = {17},
year = {2026}
}
TY - JOUR
AB - Snakebite accidents are prevalent worldwide and cause a spectrum of severe clinical manifestations and result in a reduction of patient quality of life and economic income. A major bottleneck in envenomation treatment is our limited understanding of how venom toxins perturb specific cellular processes involved in tissue necrosis. Here, we address this knowledge gap and define the cellular mechanisms via which cell death is triggered by the snake toxin L-amino acid oxidase (LAAO). LAAO is a highly toxic enzyme present in various venoms that causes tissue necrosis, edema, coagulopathies, and organ failure. Here, we identify the residues essential for LAAO oxidation and obtain a catalytically inactive LAAO mutant, which is unable to reproduce the cellular phenotypes. Striking cellular defects are triggered by a catalysis-dependent increase in oxidative stress, via H2O2 (reaction by product). LAAO uptake by cells leads to a decrease in lysosome number and size and inhibits autophagy flux. In parallel, mitochondria function is impaired by severe proton leakage, and mitochondrial fission is stimulated, causing their engulfment by autophagosomes. However, mitochondrial clearance is prevented by the lysosomal defects. The concurrent shutdown of cell respiration and energy consumption indicates that LAAO catalysis reduces both metabolism and cell fitness. Thus, essential organelles are coordinately impaired by LAAO activity, accelerating cell demise. Considering the multi-organelle impairment, strategies to reduce organelle injury after LAAO exposure may be effective to maintain critical cell functions and strengthen adaptive responses against cytotoxicity.
AU - Prak,K
AU - Luft,C
AU - Tsefou,E
AU - Chavez-Olortegui,C
AU - Kriston-Vizi,J
AU - Ketteler,R
AU - Braga,V
DO - 10.1038/s41419-025-08187-7
PY - 2026///
SN - 2041-4889
TI - Functional analyses and integrated mechanisms of cellular destruction by L-amino acid oxidase
T2 - Cell Death and Disease
UR - http://dx.doi.org/10.1038/s41419-025-08187-7
UR - https://www.nature.com/cddis/open-access
VL - 17
ER -