scholarly journals Interplay between mitochondria and diet mediates pathogen and stress resistance inC. elegans

2017 ◽  
Author(s):  
Alexey V. Revtovich ◽  
Ryan Lee ◽  
Natalia V. Kirienko
Keyword(s):  
Stress Resistance ◽  
Vitamin B12 Deficiency ◽  
E Coli ◽  
C Elegans ◽  
Mitochondrial Homeostasis ◽  
Physiological Consequence ◽  
Organismal Biology ◽  
Host Health ◽  
B12 Deficiency ◽  
Dietary Deficiency

SummaryDiet is a crucial determinant of organismal biology. Here we demonstrate the dramatic impact of a subtle shift in diet on the ability ofCaenorhabditis elegansto survive pathogenic or abiotic stress. Interestingly, this shift occurs independently of canonical host defense pathways, arising instead from improvements in mitochondrial health. Using a variety of assays, we reveal that the most commonC. elegansfood source (E. coliOP50) results in a vitamin B12 deficiency that compromises mitochondrial homeostasis. Increasing B12 supply by feeding onE. coliHT115 or by supplementing bacterial media with methylcobalamin restored mitochondrial function, even if the bacteria were dead. B12 supplementation also efficiently increased host health without adversely affecting lifespan. Our study forges a molecular link between a dietary deficiency (nutrition/microbiota) and a physiological consequence (host sensitivity), using the host-microbiota-diet framework. The ubiquity of B12 deficiency (~10-40% of US adults) highlights the importance of our findings.

scholarly journals SUMO promotes longevity and maintains mitochondrial homeostasis during ageing in Caenorhabditis elegans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Princz ◽  
Federico Pelisch ◽  
Nektarios Tavernarakis
Keyword(s):  
Caenorhabditis Elegans ◽  
Posttranslational Modifications ◽  
Stress Resistance ◽  
Important Determinant ◽  
Mitochondrial Dynamics ◽  
C Elegans ◽  
Mitochondrial Homeostasis ◽  
Somatic Tissues ◽  
Transcription Regulators ◽  
Influence Gene Expression

Abstract The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular localization of both DAF-16 and SKN-1 is further modulated by specific posttranslational modifications, such as phosphorylation and ubiquitination. Here, we show that ageing elicits a marked increase of SUMO levels in C. elegans. In turn, SUMO fine-tunes DAF-16 and SKN-1 activity in specific C. elegans somatic tissues, to enhance stress resistance. SUMOylation of DAF-16 modulates mitochondrial homeostasis by interfering with mitochondrial dynamics and mitophagy. Our findings reveal that SUMO is an important determinant of lifespan, and provide novel insight, relevant to the complexity of the signalling mechanisms that influence gene expression to govern organismal survival in metazoans.

scholarly journals OVERCOMING VITAMIN B12 DEFICIENCY IN VEGAN DIET

2014 ◽  
Vol 04 (01) ◽  
pp. 104-105
Author(s):  
Prassanna Baby ◽  
Keyword(s):  
Vitamin B12 ◽  
Higher Plants ◽  
Vitamin B12 Deficiency ◽  
Vegan Diet ◽  
Vitamin B ◽  
Daily Diet ◽  
B12 Deficiency ◽  
Vitamin B 12 ◽  
Micro Organisms ◽  
Dietary Deficiency

Abstract:Vitamin B12 is a crystalline compound essential to a number of micro-organisms and animals, including humans. So far as is known it is not present in higher plants. Pure vegetarian food is nearly free from vit. B12. It is a nutrient that needs attention in vegan diet. Vegetarians are at risk for vitamin B(12) (B12) deficiency due to suboptimal intake. Dietary deficiency of vitamin B12 due to vegetarianism is increasing and causes hyperhomocysteinemia Areas for research include intermittent vitamin B12 supplement dosing and better measurements of the bioavailability of B12 in fermented vegetarian foods and algae. The goal of the present literature review was to create an awareness among the vegans to identify the vegetarian sources of Vitamin B12 and to incorporate them into their daily diet.

scholarly journals Effects of Vitamin B12 Deficiency on Amyloid-β Toxicity in Caenorhabditis elegans

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 962
Author(s):  
Arif Andra ◽  
Shoko Tanigawa ◽  
Tomohiro Bito ◽  
Atsushi Ishihara ◽  
Fumio Watanabe ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Growth Medium ◽  
Vitamin B12 Deficiency ◽  
Amyloid Β ◽  
Aβ Peptides ◽  
C Elegans ◽  
Aβ Aggregation ◽  
B12 Deficiency ◽  
The Relationship ◽  
Aβ Production

High homocysteine (Hcy) levels, mainly caused by vitamin B12 deficiency, have been reported to induce amyloid-β (Aβ) formation and tau hyperphosphorylation in mouse models of Alzheimer’s disease. However, the relationship between B12 deficiency and Aβ aggregation is poorly understood, as is the associated mechanism. In the current study, we used the transgenic C. elegans strain GMC101, which expresses human Aβ1–42 peptides in muscle cells, to investigate the effects of B12 deficiency on Aβ aggregation–associated paralysis. C. elegans GMC101 was grown on nematode growth medium with or without B12 supplementation or with 2-O-α-D-glucopyranosyl-L-ascorbic acid (AsA-2G) supplementation. The worms were age-synchronized by hypochlorite bleaching and incubated at 20 °C. After the worms reached the young adult stage, the temperature was increased to 25 °C to induce Aβ production. Worms lacking B12 supplementation exhibited paralysis faster and more severely than those that received it. Furthermore, supplementing B12-deficient growth medium with AsA-2G rescued the paralysis phenotype. However, AsA-2G had no effect on the aggregation of Aβ peptides. Our results indicated that B12 supplementation lowered Hcy levels and alleviated Aβ toxicity, suggesting that oxidative stress caused by elevated Hcy levels is an important factor in Aβ toxicity.

scholarly journals Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Emma Watson ◽  
Viridiana Olin-Sandoval ◽  
Michael J Hoy ◽  
Chi-Hua Li ◽  
Timo Louisse ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Metabolic Network ◽  
Genetic Interaction ◽  
Vitamin B12 Deficiency ◽  
Selective Advantage ◽  
C Elegans ◽  
In The Wild ◽  
B12 Deficiency ◽  
Mapping Gene ◽  
Network Rewiring

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild.

scholarly journals Lysosomal activity regulatesCaenorhabditis elegansmitochondrial dynamics through vitamin B12 metabolism

2020 ◽  
Vol 117 (33) ◽  
pp. 19970-19981 ◽  
Author(s):  
Wei Wei ◽  
Gary Ruvkun
Keyword(s):  
Vitamin B12 ◽  
Mitochondrial Biogenesis ◽  
Energy Demand ◽  
Mitochondrial Fission ◽  
Vitamin B12 Deficiency ◽  
Periodic Pattern ◽  
C Elegans ◽  
Lysosomal Dysfunction ◽  
Methionine Restriction ◽  
B12 Deficiency

Mitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern inCaenorhabditis elegansmuscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin DRP-1. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of theC. elegansdynamin mutant on anEscherichia colistrain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the twoC. elegansenzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis, which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of thesams-1S-adenosylmethionine synthase also suppresses thedrp-1fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.

scholarly journals Lysosomal activity regulates Caenorhabditis elegans mitochondrial dynamics through vitamin B12 metabolism

2020 ◽  
Author(s):  
Wei Wei ◽  
Gary Ruvkun
Keyword(s):  
Caenorhabditis Elegans ◽  
Vitamin B12 ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Vitamin B12 Deficiency ◽  
Periodic Pattern ◽  
C Elegans ◽  
Lysosomal Dysfunction ◽  
B12 Deficiency

ABSTRACTMitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern in Caenorhabditis elegans muscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of the C. elegans dynamin mutant on an E. coli strain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the two C. elegans enzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of the sams-1 S-adenosylmethionine synthase also suppresses the drp-1 fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.SIGNIFICANCE STATEMENTThe balance of mitochondrial fission and fusion, two aspects of mitochondrial dynamics, is important for mitochondrial function. Here we show that Caenorhabditis elegans lysosomal activity regulates mitochondrial dynamics by affecting mitochondrial fission through interfering the metabolism of a micronutrient, vitamin B12. Vitamin B12 is exclusively obtained from diets in animals including C. elegans and humans, and its uptake is mediated by the lysosome. We show that lysosomal dysfunction causes vitamin B12 deficiency that leads to reduction of methionine and S-adenosylmethionine to in turn increase mitochondrial biogenesis and fission. Our study provides an insight on the interactions between mitochondrial function and micronutrient metabolism.

scholarly journals Bacterial processing of glucose modulates C. elegans lifespan and healthspan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samuel F. Kingsley ◽  
Yonghak Seo ◽  
Calista Allen ◽  
Krishna S. Ghanta ◽  
Steven Finkel ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Critical Role ◽  
Glutathione S Transferase ◽  
Negative Effects ◽  
E Coli ◽  
C Elegans ◽  
Growth Defects ◽  
Glycation End Products ◽  
Heat Stress Resistance ◽  
Dietary Sugar

AbstractIntestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a Caenorhabditis elegans-E. coli system where only the bacteria have direct contact with glucose. Our data reveal that bacterial processing of glucose results in reduced lifespan and healthspan including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. With chronic exposure to glucose, E. coli exhibits growth defects and increased advanced glycation end products. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of the glutathione-S-transferase, gst-4 shortens C. elegans lifespan and blunts the animal's response to a glucose fed bacterial diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define a critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

Balanced mRNA storage and degradation regulates mitochondrial homeostasis, ageing and stress resistance in Caenorhabditis elegans

2020 ◽  
Author(s):  
Ιωάννα Δασκαλάκη
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Resistance ◽  
C Elegans ◽  
Mitochondrial Homeostasis

Ο αριθμός των μιτοχονδρίων σε συνδυασμό με την λειτουργία τους αποτελούν σημαντικούς ρυθμιστές της υγείας των ατόμων αλλά και του προσδόκιμου ζωής αυτών σε ποικίλους οργανισμούς, από απλούς όπως ο νηματώδης C. elegans έως και πολύ πολύπλοκους όπως είναι ο άνθρωπος. Συγκεκριμένα, η διατάραξή τους συσχετίζεται συχνά με παθολογικές καταστάσεις όπως τα λυσοσωμικά αθροιστικά νοσήματα, η καρδιαγγειακή νόσος, ο νευροεκφυλισμός και σακχαρώδης διαβήτης τύπου 2, μεταξύ άλλων. Ο αριθμός των μιτοχονδρίων ελέγχεται στενά από δύο αντίθετες διαδικασίες, την βιογένεση των μιτοχονδρίων και τη μιτοφαγία. Σε αντίθεση με τη μιτοφαγία, η οποία έχει μελετηθεί εκτεταμένα, οι μηχανισμοί μιτοχονδριακής βιογένεσης εξακολουθούν να είναι ως επί το πλείστον ανεξερεύνητοι. Η ημι-αυτόνομη φύση των μιτοχονδρίων καθιστά τη βιογένεσή τους μια πολύπλοκη διαδικασία που βασίζεται στον συντονισμό σηματοδότησης από τα μιτοχόνδρια προς τον πυρήνα και από τον πυρήνα προς τα μιτοχόνδρια. Η τοπική μετάφραση των μεταγραφημάτων μιτοχονδριακών πρωτεϊνών που κωδικοποιούνται από το πυρηνικό DNA (NEMTTs) κοντά στα μιτοχόνδρια, είναι θεμελιώδης για τη βιογένεση των μιτοχονδρίων. Παρόλο που αναμένεται ότι κυτταροπλασματικοί παράγοντες θα πρέπει κυρίως να ρυθμίζουν την τοπική μετάφραση υπό κανονικές συνθήκες και ως απόκριση σε στρες, οι παράγοντες αυτοί παραμένουν ασαφείς. Στόχος της παρούσας διατριβής είναι η διαλεύκανση αυτών των παραγόντων χρησιμοποιώντας ως πρότυπο οργανισμό το C. elegans. Στα πλαίσια αυτή, αποκαλύπτουμε ότι κυτταροπλασματικοί παράγοντες που σχετίζονται με το μονοπάτι 5'-3' αποικοδόμησης των αγγελιοφόρων RNA (mRNA), αποτελούν νέους, βασικούς ρυθμιστές του αριθμού και της λειτουργίας των μιτοχονδρίων στο νηματώδη. Πιο συγκεκριμένα, δείχνουμε ότι το πρωτεϊνικό σύμπλοκο που πραγματοποιεί την αφαίρεση του καλύμματος των mRNA και τo σύμπλοκo αποαδενυλίωσης (CCR-4 / NOT) εμπεριέχονται σε ξεχωριστούς σχηματισμούς που έχουν φυσική αλληλεπίδραση με τα μιτοχόνδρια και ρυθμίζουν αντίθετα τον αριθμό τους κατά τη διάρκεια της γήρανσης. Ο μηχανισμός μέσω του οποίου επιτυγχάνουν κάτι τέτοιο βασίζεται στη μετα-μεταγραφική ρύθμιση των NEMTTs που πραγματοποιείται κοντά στο οργανίδιο. Η ισορροπημένη αποικοδόμηση και αποθήκευση των NEMTTs-στόχων είναι αναγκαία για τη ρύθμιση του αριθμού και της λειτουργίας των μιτοχονδρίων. Η επίτευξη μιας τέτοιας ισορροπίας τελικά προάγει την απόκριση σε στρες και τη μακροβιότητα ατόμων C. elegans. Τα ευρήματά μας αποκαλύπτουν ένα νέο ρόλο των παραγόντων μεταβολισμού των mRNAs στη βιογένεση των οργανιδίων και με αυτό τον τρόπο οδηγούν στην ταυτοποίηση των κυτταροπλασματικών συστατικών που συντονίζουν την τοπική μετάφραση κατά τη διάρκεια της γήρανσης και υπό συνθήκες στρες στο C. elegans.

scholarly journals Bacterial processing of glucose modulates C. elegans lifespan and healthspan

2020 ◽  
Author(s):  
Samuel F. Kingsley ◽  
Yonghak Seo ◽  
Calista Allen ◽  
Krishna S. Ghanta ◽  
Steven Finkel ◽  
...  
Keyword(s):  
Stress Resistance ◽  
Critical Role ◽  
Glutathione S Transferase ◽  
Negative Effects ◽  
E Coli ◽  
C Elegans ◽  
Growth Defects ◽  
Glycation End Products ◽  
Heat Stress Resistance ◽  
Dietary Sugar

AbstractIntestinal microbiota play an essential role in the health of a host organism. Here, we define how commensal Escherichia coli (E. coli) alters its host after long term exposure to glucose using a C. elegans-E. coli system. Our data reveal that bacterial processing of glucose, rather than direct ingestion by the animal, results in reduced lifespan and healthspan, including reduced locomotion, oxidative stress resistance, and heat stress resistance in C. elegans. Chronic exposure of E. coli to glucose produces growth defects and increased advanced glycation end products within the E. coli. These negative effects are abrogated when the E. coli is not able to process the additional glucose and by the addition of the anti-glycation compound carnosine. Physiological changes of the host C. elegans are accompanied by dysregulation of detoxifying genes including glyoxalase, glutathione-S-transferase, and superoxide dismutase. Loss of gst-4 shortens C. elegans lifespan and blunts the animal’s response to a glucose-fed bacteria diet. Taken together, we reveal that added dietary sugar may alter intestinal microbial E. coli to decrease lifespan and healthspan of the host and define the critical role of detoxification genes in maintaining health during a chronic high-sugar diet.

scholarly journals Tongue disorders due to megaloblastic anaemia and its management: A case report.

2021 ◽  
Vol 11 (1) ◽  
pp. 26-28
Author(s):  
Md Ashif Iqbal ◽  
Rina Niroula ◽  
Prima Singh ◽  
Mehnaz Khan
Keyword(s):  
Vitamin B12 ◽  
Vitamin B12 Deficiency ◽  
Signs And Symptoms ◽  
Folic Acid Supplementation ◽  
Megaloblastic Anaemia ◽  
Burning Sensation ◽  
Blood Picture ◽  
B12 Deficiency ◽  
Folate And Vitamin B12 ◽  
Dietary Deficiency

The presence of megaloblasts and macrocytes in the bone marrow characterizes megaloblastic anaemia. Megaloblastic anaemia is the result of folate and vitamin B12 deficiency in more than 95% of cases. We hereby report a case of megaloblastic anaemia in a 23-year old female having glossitis and a burning sensation on the tongue. The blood picture showed megaloblastic anaemia and haematological tests confirmed the diagnosis. The patient positively responded to vitamin B12 and folic acid supplementation. The presence of oral signs and symptoms offer the dentist an opportunity to participate in the diagnosis of this condition. Early diagnosis is important to prevent deficiency. This paper explains the oral changes induced by dietary deficiency of cobalamin or folate in a patient with megaloblastic anaemia. Update Dent. Coll. j: 2021; 11 (1): 26-28

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