2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism

2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism Olha M. Strilbytska, Uliana Semaniuk, Ihor Yurkevych, Andriy Glovyak, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4859683/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Uncouplers of mitochondrial electron transport chain, such as 2,4-dinitrophehol (DNP), can mimic calorie restriction by decreasing efficiency of adenosine triphosphate (ATP) synthesis. However, DNP is also a toxic substance, whose overdosage can be lethal. In the fruit fly, Drosophila melanogaster model, we have found that DNP in concentrations of 0.05–0.2 g/L, led to a drastic decrease in fruit fly survival on a low caloric diet (1% sucrose and 1% yeast; 1S-1Y). On the 5S-5Y diet, DNP decreased lifespan of flies reared only in concentration 0.2 g/L, whilst on the diet 15S-15Y DNP either did not significantly shortened fruit fly lifespan or extended it. The lifespan extension on the high caloric 15S-15Y diet with DNP was accompanied by lower activity of lactate dehydrogenase and a decrease in activities of mitochondrial respiratory chain complexes I, II, and V, determined by blue native electrophoresis followed by in-gel activity assays. The exposure to DNP also did not affect key glycolytic enzymes, antioxidant and related enzymes, and markers of oxidative stress, such as aconitase activity and amount protein carbonyls. Consumption of DNP-supplemented diet did not affect flies’ resistance to heat stress, though made male flies slightly more resistant to starvation compared with males reared on the control food. We also did not observe substantial changes in the contents of metabolic stores, triacylglycerols and glycogen, in the DNP-treated flies. All this suggest that a nutrient-rich diets provide effective protection against DNP, providing a mild uncoupling of the respiratory chain that allows lifespan extension without considerable changes in metabolism. uncoupler mitochondria Drosophila melanogaster lifespan metabolism blue native electrophoresis Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 14 Aug, 2024 Reviews received at journal 13 Aug, 2024 Reviews received at journal 12 Aug, 2024 Reviewers agreed at journal 09 Aug, 2024 Reviewers agreed at journal 09 Aug, 2024 Reviewers invited by journal 09 Aug, 2024 Editor assigned by journal 05 Aug, 2024 Submission checks completed at journal 05 Aug, 2024 First submitted to journal 05 Aug, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4859683","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":340208465,"identity":"f3568297-497e-40ba-af0f-4023814a0ef6","order_by":0,"name":"Olha M. 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However, DNP is also a toxic substance, whose overdosage can be lethal. In the fruit fly, \u003cem\u003eDrosophila melanogaster\u003c/em\u003e model, we have found that DNP in concentrations of 0.05\u0026ndash;0.2 g/L, led to a drastic decrease in fruit fly survival on a low caloric diet (1% sucrose and 1% yeast; 1S-1Y). On the 5S-5Y diet, DNP decreased lifespan of flies reared only in concentration 0.2 g/L, whilst on the diet 15S-15Y DNP either did not significantly shortened fruit fly lifespan or extended it. The lifespan extension on the high caloric 15S-15Y diet with DNP was accompanied by lower activity of lactate dehydrogenase and a decrease in activities of mitochondrial respiratory chain complexes I, II, and V, determined by blue native electrophoresis followed by in-gel activity assays. The exposure to DNP also did not affect key glycolytic enzymes, antioxidant and related enzymes, and markers of oxidative stress, such as aconitase activity and amount protein carbonyls. Consumption of DNP-supplemented diet did not affect flies\u0026rsquo; resistance to heat stress, though made male flies slightly more resistant to starvation compared with males reared on the control food. We also did not observe substantial changes in the contents of metabolic stores, triacylglycerols and glycogen, in the DNP-treated flies. All this suggest that a nutrient-rich diets provide effective protection against DNP, providing a mild uncoupling of the respiratory chain that allows lifespan extension without considerable changes in metabolism.\u003c/p\u003e","manuscriptTitle":"2,4-Dinitrophenol is toxic on a low caloric diet but extends lifespan of Drosophila melanogaster on nutrient-rich diets without an impact on metabolism","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-30 17:07:51","doi":"10.21203/rs.3.rs-4859683/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-14T11:27:26+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-14T00:24:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-12T23:33:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321907165091426958103935376174945902578","date":"2024-08-09T17:02:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276570426921218840489469403109515110251","date":"2024-08-09T14:06:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-08-09T12:34:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-08-05T17:50:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-05T06:51:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Biogerontology","date":"2024-08-05T06:32:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"biogerontology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Biogerontology](https://www.springer.com/journal/10522)","snPcode":"10522","submissionUrl":"https://submission.nature.com/new-submission/10522/3","title":"Biogerontology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"b6510de2-f2f0-46f7-8700-61c377401c48","owner":[],"postedDate":"August 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-12-06T18:23:12+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-30 17:07:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4859683","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4859683","identity":"rs-4859683","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}