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- W2024398514 abstract "Mitochondrial DNA (mtDNA) T8993G mutation inhibits specifically mitochondrial F1F0-ATPase (complex V) for severe ATP deficiency and is clinically associated with neurological muscle weakness, ataxia, and retinitis pigmentosa so called NARP mutation. At present, detail T8993G-associated mitochondrial mechanisms as well as its therapeutic strategies are limited. Using time-lapse laser scanning dual fluorescence imaging microscopy, this study investigated T8993G-altered apoptotic mitochondrial pathology particular upon mCa2+ stress and protection by melatonin, previously reported to protect mCa2+ stress-mediated apoptosis (Hsu et al., 2009 JPR in press). In comparison to its parental osteosarcoma 143B and mtDNA less (ρ0) cells, T8993G induced significant hyperpolarization of mitochondrial membrane potential (ΔΨm) and potentiated greatly ionomycin-induced mCa2+ stress. T8993G-augmented mCa2+ stress subsequently elicited rigorously generation of mitochondrial oxygen species (mROS), depletion of cardiolipin (CL) and activation of the mitochondrial permeability transition (MPT). In contract, ρ0 cells, with much depolarized ΔΨm, suffered less mCa2+ stress, mROS formation, CL depletion and the MPT opening. Interestingly, melatonin reduced significantly peak amplitude of the ionomycin-induced mCa2+ transient and antagonized efficiently mCa2+-augmented mROS generation for a reduced depletion of CL and activation of the MPT. In addition, melatonin prevented “oxidation free mCa2+”-mediated MPT suggesting its direct targeting on the MPT. Melatonin-enhanced tail amplitude of mCa2+ transient possibly due to the reduced MPT-dependent depolarization of ΔΨm, however, did not enhance mCa2+ stress-mediated pathology in NARP cybrids possibly as melatonin-elevated mCa2+ improved mitochondrial respiratory. Thus, the administration of melatonin may provide potential improvement for the treatment of mtDNA T8993G-associated NARP syndromes and diseases." @default.
- W2024398514 created "2016-06-24" @default.
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- W2024398514 date "2010-01-01" @default.
- W2024398514 modified "2023-10-18" @default.
- W2024398514 title "mtDNA T8993G-Augmented Mitochondrial Stresses Upon mCa2+ Overload and its Protection by Melatonin in a NARP Cybrid" @default.
- W2024398514 doi "https://doi.org/10.1016/j.bpj.2009.12.2037" @default.
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