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Mitochondrial dynamics: Shaping and remodeling an organelle network.

ABSTRACT: Mitochondria form networks that continually remodel and adapt to carry out their cellular function. The mitochondrial network is remodeled through changes in mitochondrial morphology, number, and distribution within the cell. Mitochondrial dynamics depend directly on fission, fusion, shape transition, and transport or tethering along the cytoskeleton. Over the past several years, many of the mechanisms underlying these processes have been uncovered. It has become clear that each process is precisely and contextually regulated within the cell. Here, we discuss the mechanisms regulating each aspect of mitochondrial dynamics, which together shape the network as a whole.

SUBMITTER: Fenton AR

PROVIDER: S-EPMC7925334 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Mitochondrial dynamics: Shaping and remodeling an organelle network.

Fenton Adam R AR Jongens Thomas A TA Holzbaur Erika L F ELF

Current opinion in cell biology 20200919

Mitochondria form networks that continually remodel and adapt to carry out their cellular function. The mitochondrial network is remodeled through changes in mitochondrial morphology, number, and distribution within the cell. Mitochondrial dynamics depend directly on fission, fusion, shape transition, and transport or tethering along the cytoskeleton. Over the past several years, many of the mechanisms underlying these processes have been uncovered. It has become clear that each process is preci ...[more]

PMID: 32961383

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Project description:IntroductionNeurological dysfunction induced by fluoride contamination is still one of major concern worldwide. Recently, neuroprotective roles of silent information regulator 1 (SIRT1) focusing on mitochondrial function have been highlighted. However, what roles SIRT1 exerts and the underlying regulative mechanisms, remain largely uncharacterized in such neurotoxic process of fluoride.ObjectivesWe aimed at evaluating the regulatory roles of SIRT1 in human neuroblastoma SH-SY5Y cells and Sprague-Dawley rats with fluoride treatment, and to further identify potential miRNA directly targeting SIRT1.MethodsPharmacological suppression of SIRT1 by nicotinamide (NIC) and promotion of SIRT1 by adenovirus (Ad-SIRT1) or resveratrol (RSV) were employed to assess the effects of SIRT1 in mitochondrial dysfunction induced by fluoride. Also, miRNAs profiling and bioinformatic prediction were used to screen the miRNAs which can regulate SIRT1 directly. Further, chemical mimic or inhibitor of chosen miRNA was applied to validate the modulation of chosen miRNA.ResultsNIC exacerbated defects in mitochondrial network dynamics and cytochrome c (Cyto C) release-driven apoptosis, contributing to fluoride-induced neuronal death. In contrast, the ameliorative effects were observed when overexpressing SIRT1 by Ad-SIRT1 in vitro or RSV in vivo. More importantly, miR-708-3p targeting SIRT1 directly was identified. And interestingly, moreover, treatment with chemically modified miR-708-3p mimic aggravated, while miR-708-3p inhibitor suppressed fluoride-caused neuronal death. Further confirmedly, overexpressing SIRT1 effectively neutralized miR-708-3p mimic-worsened fluoride neuronal death via correcting mitochondrial network dynamics. On contrary, inhibiting SIRT1 counteracted the promotive effects of miR-708-3p inhibitor against neurotoxic response by fluoride through aggravating abnormal mitochondrial network dynamics.ConclusionThese data underscore the functional importance of SIRT1 to mitochondrial network dynamics in neurotoxic process of fluoride and further screen a novel unreported neuronal function of miR-708-3p as an upstream regulator of targeting SIRT1, which has important theoretical implications for a potential therapeutic and preventative target for treatment of neurotoxic progression by fluoride.

Dataset Information

Mitochondrial dynamics: Shaping and remodeling an organelle network.

Publications

Mitochondrial dynamics: Shaping and remodeling an organelle network.

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