Severe burn-induced mitochondria recruitment of calpain causes aberrant
of mitochondrial dynamics and heart dysfunction
Mitochondria damage is an important cause of heart dysfunction after
severe burn. However, the pathophysiological process remains unclear.
This study aims to examine the mitochondrial dynamics in the heart after
severe burn, and the role of μ-calpain, a cysteine protease, in this
scenario. Rats were subjected to thermal injury treatment, and calpain
inhibitor MDL28170 was given intravenously 1 h before burn injury.
Compared with the sham group, the rats in the burn group displayed
weakened heart performance and decreased mean arterial pressure, which
was accompanied by a diminishment of mitochondria function. Furthermore,
severe burn increased the level of calpain in mitochondria, reflected by
immunofluorescence staining and activity test. In contrast, treatment
with MDL28170 diminished these responses to a severe burn. Severe burn
induced morphological defects of mitochondria, and decreased the
abundance of mitochondria. Of note, severe burn increased the percentage
of the mitochondria with bigger size, but decreased the smaller ones.
Analysis of dynamic proteins revealed that severe burn caused an
increase of fission protein DRP1 in the mitochondria and a decrease of
inner membrane fusion protein OPA1. Similarly, these alterations were
also blocked by MDL28170. Last but not the least, inhibition of calpain
yielded the emergence of more elongated mitochondria along with membrane
invagination in the middle of the longitude, an indicator of the fission
process. Overall, these results for the first time provide evidence that
mitochondria recruitment of calpain confers heart dysfunction after
severe burn, which involves mitochondrial dynamics damage.