<scp>SEMO</scp>‐1, a novel methanethiol oxidase in <i>Caenorhabditis elegans</i>, is a pro‐aging factor conferring selective stress resistance

Philipp, Thilo Magnus; Gong, Weiye; Köhnlein, Karl; Ohse, Verena Alexia; Müller, Frederike Iris; Priebs, Josephine; Steinbrenner, Holger; Klotz, Lars‐Oliver

doi:10.1002/biof.1836

Cited by 13 publications

(23 citation statements)

References 31 publications

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“…Surprisingly, we also observed a rapid increase in the expression of genes associated with intracellular H 2 S production, such as semo-1 and mpst-3 genes ( Figure 3E and F, Figure 3—figure supplement 1D and E ) (Philipp et al, 2022; Qabazard et al, 2014). However, these data aligned with earlier observations made in sulfide spring fish (Kelley et al, 2016; Mathew, Schlipalius, & Ebert, 2011; Qabazard et al, 2014).…”

Section: Resultsmentioning

confidence: 81%

Acute avoidance of hydrogen sulfide is modulated by external and internal states inC. elegans

Pu,

Zhao,

Wang

et al. 2023

Preprint

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Hydrogen sulfide (H2S) can act as an energy source, a poison and a gasotransmitter in organisms. We used the robust locomotory responses to H2S inCaenorhabditis elegansto delineate the molecular mechanisms governing sensory and adaptive responses to H2S exposure. We found thatC. elegansexhibited transiently increased locomotory activity and turning behavior as a strategy to escape the noxious H2S stimulation. The behavioral responses to H2S were modulated by a complex network of signaling pathways, including cyclic GMP signaling in ciliated sensory neurons, calcineurin, nuclear hormone receptors, to the major starvation regulators such as insulin and TGF-β signaling. The response to H2S was substantially affected by the ambient O2levels and their prior experience in low O2environments, suggesting an intricate interplay between O2and H2S sensing mechanisms. Prolonged exposure to H2S robustly evoked H2S detoxification coupled with reduced locomotory response to the subsequent H2S challenges. Intriguingly, the expression of genes involved in iron homeostasis, includingftn-1andsmf-3, was substantially modified in exposure to H2S, implying that labile iron levels are affected by H2S. In support of this, iron supplement significantly bolstered the behavioral response to H2S. In addition, mitochondria, one of the central hubs for H2S metabolism, played a crucial role in adaptive responses to H2S. In summary, our study provides molecular insights into the mechanisms through whichC. elegansdetects, modulates, and adapts its response to H2S.

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Section: Resultsmentioning

confidence: 81%

Acute avoidance of hydrogen sulfide is modulated by external and internal states inC. elegans

Pu,

Zhao,

Wang

et al. 2023

Preprint

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“…Plasmids for C. elegans hyp7-specific expression used the promoter from semo-1/Y37A1B.5 (P hyp-7 ) (118). Vector details are available upon request.…”

Section: Methodsmentioning

confidence: 99%

Conserved NIMA kinases regulate multiple steps of endocytic trafficking

Joseph

Naslavsky

Binti

et al. 2022

Preprint

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Human NIMA-related kinases have primarily been studied for their roles in cell cycle progression (NEK1/2/6/7/9), checkpoint-DNA-damage control (NEK1/2/4/5/10/11), and ciliogenesis (NEK1/4/8). We previously showed that Caenorhabditis elegans NEKL-2 (NEK8/9 homolog) and NEKL-3 (NEK6/7 homolog) regulate apical clathrin-mediated endocytosis (CME) in the worm epidermis and are essential for molting. Here we show that NEKL-2 and NEKL-3 also have distinct roles in controlling endosome function and morphology. Specifically, loss of NEKL-2 led to enlarged early endosomes with long tubular extensions but showed minimal effects on other compartments. In contrast, NEKL-3 depletion caused pronounced defects in early, late, and recycling endosomes. Consistently, NEKL-2 was strongly localized to early endosomes, whereas NEKL-3 was localized to multiple endosomal compartments. Loss of NEKLs also led to variable defects in the recycling of two resident cargoes of the trans-Golgi network (TGN), MIG-14/Wntless and TGN-38/TGN38, which were missorted to lysosomes after NEKL depletion. In addition, defects were observed in the uptake of clathrin-dependent (SMA-6/Type I BMP receptor) and independent cargoes (DAF-4/Type II BMP receptor) from the basolateral surface of epidermal cells after NEKL-2 or NEKL-3 depletion. Complementary studies in human cell lines further showed that siRNA knockdown of the NEKL-3 orthologs NEK6 and NEK7 led to missorting of the mannose 6-phosphate receptor from endosomes. Moreover, in multiple human cell types, depletion of NEK6 or NEK7 disrupted both early and recycling endosomal compartments, including the presence of excess tubulation within recycling endosomes, a defect also observed after NEKL-3 depletion in worms. Thus, NIMA family kinases carry out multiple functions during endocytosis in both worms and humans, consistent with our previous observation that human NEKL-3 orthologs can rescue molting and trafficking defects in C. elegans nekl-3 mutants. Our findings suggest that trafficking defects could underlie some of the proposed roles for NEK kinases in human disease.

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“…C. elegans expression plasmids utilized the Phyp-7 promoter from the semo-1 gene for hypodermal expression, or the Pmec-7 promoter from the mec-7 gene for touch neuron expression [15, 55, 56]. Vector details are available upon request.…”

Section: Methodsmentioning

confidence: 99%

“…Recycling of material not destined for degradation, such as phagocytic receptors, proceeds at the same time. To determine if mCherry-containing exophers undergo phagocytosis and phagosome maturation in the surrounding hypodermis, we expressed a variety of molecular markers with mNeonGreen tags from single copy transgenes using a hypodermis specific promoter (Phyp7) from the semo-1/Y37A1B.5 gene [15].…”

Section: Neuronal Exophers Undergo Phagocytosis By the Hypodermismentioning

confidence: 99%

Large vesicle extrusions fromC. elegansneurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell

Wang

Arnold

Smart

et al. 2022

Preprint

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C. elegans neurons under stress can produce giant vesicles, several microns in diameter, called exophers. Current models suggest that exophers are neuroprotective, providing a mechanism for stressed neurons to eject toxic protein aggregates and organelles. However, little is known of the fate of the exopher once it leaves the neuron. We found that exophers produced by mechanosensory neurons in C. elegans are engulfed by surrounding hypodermal skin cells, and are then broken up into numerous smaller vesicles that acquire hypodermal phagosome maturation markers, with vesicular contents gradually degraded by hypodermal lysosomes. Consistent with the hypodermis acting as an exopher phagocyte, we found that the hypodermal plasma membrane adjacent to newly formed exophers surrounds the exopher and accumulates F-actin. Efficient fission of engulfed exopher-phagosomes to produce smaller vesicles and degrade their contents required phagosome maturation factors SAND-1/Mon1, GTPase RAB-35, the CNT-1 ARF-GAP, and microtubule motor associated GTPase ARL-8, suggesting a close coupling of phagosome fission and phagosome maturation. Lysosome activity was required to degrade exopher contents in the hypodermis but not for exopher-phagosome resolution into smaller vesicles. Importantly, we found that GTPase ARF-6 and effector SEC-10/Exocyst activity in the hypodermis, along with the CED-1 phagocytic receptor, is required for efficient production of exophers by the neuron. Our results indicate that the neuron requires specific interaction with the phagocyte for an efficient exopher response, a mechanistic feature potentially conserved with mammalian exophergenesis, and similar to neuronal pruning by phagocytic glia that influences neurodegenerative disease.

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SEMO‐1, a novel methanethiol oxidase in Caenorhabditis elegans, is a pro‐aging factor conferring selective stress resistance

Cited by 13 publications

References 31 publications

Acute avoidance of hydrogen sulfide is modulated by external and internal states inC. elegans

Acute avoidance of hydrogen sulfide is modulated by external and internal states inC. elegans

Conserved NIMA kinases regulate multiple steps of endocytic trafficking

Large vesicle extrusions fromC. elegansneurons are consumed and stimulated by glial-like phagocytosis activity of the neighboring cell

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