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Schema of GAPDH aggregate-induced mitochondrial dysfunction. Aggregates of GAPDH are formed at mitochondria, which directly induce a decrease in mitochondrial membrane potential (Δψ) and mitochondrial swelling via the opening of a PTP. Mitochondrial dysfunction results in both cytosolic release of cyt c and nuclear translocation of AIF, leading to necrosis. Meanwhile, aggregates of GAPDH do not influence proteasome activity, the ER stress cascade, or the induction of autophagy.
