ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in Drosophila

Liao, Pin-Chao; Tandarich, Lauren C.; Hollenbeck, Peter J.

doi:10.1371/journal.pone.0178105

Cited by 44 publications

(37 citation statements)

References 68 publications

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“…For particles that move quickly, kymographic analysis supports that the movement is microtubule based (Fig. 1B, C) (Liao et al, 2017). Adding the microtubule destabilizer colcemide causes particles and mitochondria to remain completely stationary, as well as disrupts the microtubule cytoskeleton as expected (Supp.…”

Section: Clu Particles Are Abundant and Highly Dynamicsupporting

confidence: 68%

Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress

Sheard

Thibault-Sennett

Sen

et al. 2019

Preprint

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Mitochondria perform a myriad of biochemical functions in the cell that integrate ATP production and metabolism. While mitochondria contain their own genome, mtDNA, it only encodes thirteen proteins required for oxidative phosphorylation, thus well over one thousand proteins required for all mitochondrial functions are encoded in the nucleus. One such protein is Drosophila Clueless (Clu), whose vertebrate homolog is Clustered mitochondria homolog (Cluh). Clu/Cluh is a ribonucleoprotein that regulates mRNAs destined for import into mitochondria and is an essential protein that regulates cellular metabolism. Clu forms large particles in the cytoplasm, although how these particles relate to nutrition and metabolic stress is unknown. Using liveimaging, we show Clu particles are highly dynamic. Clu particles appear to be unique as they do not colocalize with many known cytoplasmic bodies. In addition, Clu particle formation is highly dependent on diet as ovaries from starved females no longer contain Clu particles although Clu protein levels remain the same and insulin is necessary and sufficient for Clu particle formation. Oxidative stress also disperses particle. Since Clu particles are only present under optimal conditions we are naming them bliss particles. These observations identify Clu particles as unique, stress-sensitive cytoplasmic ribonucleoprotein particles whose absence corresponds with altered mitochondrial function and localization.

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Section: Clu Particles Are Abundant and Highly Dynamicsupporting

confidence: 68%

Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress

Sheard

Thibault-Sennett

Sen

et al. 2019

Preprint

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“…In the final phase of the writing of this manuscript, a paper came out on oxidative stress (paraquat and H 2 O 2 ) induced motility inhibition in fly neurons (Liao et al, 2017). Thus, ROS control motility both in fly and mammalian cells, though in fly, the ROS effect seems to be mediated via [Ca 2+ ] c elevation, whereas in mammalian cells, ROS can engage robust motility inhibition even independent of Ca 2+ .…”

Section: Discussionmentioning

confidence: 99%

ROS Control Mitochondrial Motility through p38 and the Motor Adaptor Miro/Trak

et al. 2017

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Summary Mitochondrial distribution and motility are recognized as central to many cellular functions but their regulation by signaling mechanisms remains to be elucidated. Here we report that ROS, either derived from an extracellular source or intracellularly generated, controls mitochondrial distribution and function, by dose-dependently, specifically and reversibly decreasing mitochondrial motility in both rat hippocampal primary cultured neurons and cell lines. ROS decrease motility independently of cytoplasmic [Ca2+], mitochondrial membrane potential or permeability transition pore opening, known effectors of oxidative stress. However, multiple lines of genetic and pharmacological evidence support that a ROS-activated MAP kinase, p38α is required for the motility inhibition. Furthermore, anchoring mitochondria directly to kinesins without involvement of the physiological adaptors between the organelles and the motor protein prevents the H2O2–induced decrease in mitochondrial motility. Thus, ROS engage p38α and the motor adaptor complex to exert changes in mitochondrial motility, which likely has both physiological and pathophysiological relevance.

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“…In previous work, the reduction in the motility of intracellular organelles was detected without morphological changes of cells under a phase contrast microscope (Sakuma et al, 2016). This is supported by the result that the motility of mitochondria was suppressed by cell damage (Debattisti et al, 2017; Liao et al, 2017). The motility of mitochondria gradually decreased just after the addition of hydrogen peroxide, and the decrease in the motility reached 50% within 10 minutes (Debattisti et al, 2017).…”

Section: Introductionmentioning

confidence: 65%

Quantitative Detection of Cell Activity by Measuring the Fluctuation of Intracellular Motility

Sakuma

Kondo

Higuchi

2019

Preprint

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13The measurement of cell activity changes during damage is important to 14 understand the process of cell death and evaluate the effect of medicines. To 15 evaluate cell activity generally, we extended the method of intensity fluctuation in 16 which intensity change in the pixel induced by the movement of organelles was 17 calculated. Cancer, endothelial and iPS cells were damaged by reactive oxygen 18 species (ROS) generated by a fluorescent dye (IR700), hydrogen peroxide, and 19 ultraviolet light. The intensity fluctuation in damaged cells gradually decreased 20 independent of the kind of cell, indicating that the decrease in the fluctuation is a 21 general phenomenon in damaged cells. The rupture of vesicles and 22 mitochondria in the cells were observed upon ROS production. The motility of 23 purified kinesin and dynein which transport vesicles and organelles was inhibited 24 by ROS. These suggest that ROS and cytotoxic molecules spreading from 25 ruptured organelles contribute to the reduction in cell activity which brings about 26 the decrease in the motility and intensity fluctuation of organelles driven by 27 kinesin and dynein.28 Liao et al., 2017). The motility of mitochondria gradually decreased just after the 65 addition of hydrogen peroxide, and the decrease in the motility reached 50% 66 within 10 minutes (Debattisti et al., 2017). These results suggested that the 67 effect on the motility of organelles in damaged cells occurred earlier than the 68 changes in cell morphology and motility. Thus, the method of detecting 69 intracellular motility under a conventional microscope would overcome the 70 disadvantages of previous fluorescence, morphological, and cell motility 71 methods. However, little is understood about the generality and mechanism of 72 motility reduction. 73In this study, various cells were damaged by several methods, including 74 photoactivation of IR700, irradiation with ultraviolet (UV) light and treatment with 75 hydrogen peroxide (H 2 O 2 ), and the change in the motility of organelles was 76 quantitatively evaluated by the developed intensity fluctuation method (IFM). We 77 found that all cells showed a decrease in motility caused by damage. To 78 elucidate the mechanisms of the decrease in motility in damaged cells, we 79 measured the reduction in the motile speeds of single vesicles in cells and in 80 purified kinesin and dynein in vitro assays. These measurements revealed that 81 the decrease detected by IMF resulted in the reduction in the organelle motility 82 driven by motor proteins. Since the transport system commonly exists in animal 83 cells, the decrease in the motility or transport of organelles would be a universal 84 phenomenon in various kinds of cells. 85 5 Results 86 87 1 Decrement of motility of organelles in damaged cells 88 Changes in the motility of organelles in damaged cells were evaluated 89 by the intensity fluctuation method (IFM) in various cell types. Six kinds of cells, 90 four cancer cell lines, one endothelial cell line, and one iPS cell line...

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ROS regulation of axonal mitochondrial transport is mediated by Ca2+ and JNK in Drosophila

Cited by 44 publications

References 68 publications

Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress

Clueless forms dynamic, insulin-responsive bliss particles sensitive to stress

ROS Control Mitochondrial Motility through p38 and the Motor Adaptor Miro/Trak

Quantitative Detection of Cell Activity by Measuring the Fluctuation of Intracellular Motility

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