SERCA2 deficiency in tubular epithelial cells drives ferroptosis in acute kidney injury regulating endoplasmic reticulum mitochondrial calcium homeostasis via voltage dependent anion channel 1 oligome

4 hours ago

SERCA2 expression is reduced in proximal tubules of patients and animal models with acute kidney injury (AKI).
SERCA2 deficiency disrupts endoplasmic reticulum calcium homeostasis, promoting VDAC1 oligomerization via impaired mitochondria-associated endoplasmic reticulum membranes.
This leads to mitochondrial permeability transition pore opening, calcium overload, oxidative stress, and ferroptosis in tubular epithelial cells.
SERCA2 activation or inhibition of VDAC1 oligomerization attenuates AKI injury, identifying this axis as a therapeutic target.

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