Inhibition of mitochondrial permeability transition pore opening is involved in the protective effects of mortalin overexpression against beta-amyloid-induced apoptosis in SH-SY5Y cells

Down-regulation of Mortalin Exacerbates Aβ-mediated Mitochondrial Fragmentation and Dysfunction

“…7). Recently, it was shown that ectopic expression of mortalin attenuates A␤-mediated oxidative stress and neurotoxicity, whereas the suppression of mortalin promotes mitochondrial dysfunction and neuronal injury (60,61). According to previous results (60, 61), we also observed that the knockdown (by siRNA) and inhibition (by MKT077) of mortalin potentiated A␤-induced mitochondrial dysfunction and cell death (Fig.…”

Involvement of mortalin/GRP75/mthsp70 in the mitochondrial impairments induced by A53T mutant α-synuclein

“…But quite different from PD, several studies suggest mortalin highly expressed in AD patients and AD models induced by β-amyloid protein (Aβ). The following studies about mechanism indicate that mortalin overexpression alleviates the Aβ-induced neurotoxicity through a mitochondria-dependent mechanism, including inhibiting the activation of mitochondrial permeability transition pore (mPTP), improving mitochondrial function, and the reducing oxidative stress (Qu et al, 2012(Qu et al, , 2011. Furthermore, in conditions mimicking PD induced by H 2 O 2 or 6-hydroxydopamine, mortalin overexpression seems to attenuate the mitochondrial injury and cell apoptosis (Chiasserini, 2010;Yang et al, 2011aYang et al, , 2011b, similar to the results detected in glucose deprivation conditions or AD models.…”

Mortalin – a multipotent chaperone regulating cellular processes ranging from viral infection to neurodegeneration

“…The oxidative stress, one of the hallmarks of neurodegenerative diseases like AD and PD, is connected to mitochondrial dysfunction (Mancuso et al, 2010). In a cellular model oxidative stress can be prevented by increased levels of mortalin (Qu et al, 2011(Qu et al, , 2012. Thus, interplay between herpesvirus re-activation and secondary infections, oxidative stress, mitochondrial dysfunction and altered levels of mortalin in AD provide a new paradigm for identification of pathomechanisms leading to AD and also to other neurodegenerative disorders.…”

“…Exposure to sub-lethal levels of Aβ led to defects in the import of mortalin and other components of the import machinery into mitochondria, which resulted in decreased mitochondrial membrane potential, increase in the levels of reactive oxygen species (ROS), increased vulnerability to oxygen-glucose deprivation and altered mitochondrial morphology (Sirk et al, 2007). Increased levels of mortalin were shown to protect cells against Aβ (1-42) -induced depolarization of mitochondrial membrane potential, reversed the reduction in cytochrome c oxidase activity and suppression of mitochondrial apoptotic cascade, and suppressed the Aβ (1-42) -induced reactive oxygen species accumulation and lipid peroxidation (Qu et al, 2011(Qu et al, , 2012.…”