{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:19:04Z","timestamp":1763990344249,"version":"3.45.0"},"reference-count":67,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inhibition of respiratory chain complex I (NADH dehydrogenase) is a widely encountered biochemical consequence of drug intoxication and a primary consequence of mtDNA mutations and other mitochondrial defects. In an organ-selective form, it is also deployed as antidiabetic pharmacological treatment. Complex I inhibition evokes a pronounced metabolic reprogramming of uncertain purposefulness, as in several cases, anabolism appears to be fostered in a state of bioenergetic shortage. A hallmark of complex I inhibition is the enhanced biosynthesis of serine, usually accompanied by an induction of folate-converting enzymes. Here, we have revisited the differential transcriptional induction of these metabolic pathways in three published models of selective complex I inhibition: MPP-treated neuronal cells, methionine-restricted rats, and patient fibroblasts harboring an NDUFS2 mutation. We find that in a coupled fashion, serinogenesis and circular folate cycling provide an unrecognized alternative pathway of complete glucose oxidation that is mostly dependent on NADP instead of the canonic NAD cofactor (NADP:NAD \u2248 2:1) and thus evades the shortage of oxidized NAD produced by complex I inhibition. In contrast, serine utilization for anabolic purposes and C1-folate provision for S-adenosyl-methionine production and transsulfuration cannot explain the observed transcriptional patterns, while C1-folate provision for purine biosynthesis did occur in some models, albeit not universally. We conclude that catabolic glucose oxidation to CO2, linked with NADPH production for indirect downstream respiration through fatty acid cycling, is the general purpose of the remarkably strong induction of serinogenesis after complex I inhibition.<\/jats:p>","DOI":"10.3390\/ijms262311349","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:09:25Z","timestamp":1763989765000},"page":"11349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2081-1170","authenticated-orcid":false,"given":"Roman","family":"Abrosimov","sequence":"first","affiliation":[{"name":"Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8858-1388","authenticated-orcid":false,"given":"Ankush","family":"Borlepawar","sequence":"additional","affiliation":[{"name":"Cellular Adaptation and Bioenergetics, Institute for Translational Medicine, MSH Medical School, 20457 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parvana","family":"Hajieva","sequence":"additional","affiliation":[{"name":"Cellular Adaptation and Bioenergetics, Institute for Translational Medicine, MSH Medical School, 20457 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7703-7712","authenticated-orcid":false,"given":"Bernd","family":"Moosmann","sequence":"additional","affiliation":[{"name":"Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany"},{"name":"Institute for Quantitative and Computational Biosciences, Johannes Gutenberg University, 55128 Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00204-020-02970-5","article-title":"Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors","volume":"95","author":"Delp","year":"2021","journal-title":"Arch. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/S0005-2728(98)00029-2","article-title":"Inhibitors of NADH-ubiquinone reductase: An overview","volume":"1364","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schiller, J., and Zickermann, V. (2022). Binding of Natural Inhibitors to Respiratory Complex I. Pharmaceuticals, 15.","DOI":"10.3390\/ph15091088"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"102838","DOI":"10.1016\/j.jbc.2022.102838","article-title":"Regulation and function of the mammalian tricarboxylic acid cycle","volume":"299","author":"Arnold","year":"2023","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2016.04.001","article-title":"Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling","volume":"100","author":"Brand","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1608400","DOI":"10.3389\/fcell.2025.1608400","article-title":"Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal","volume":"13","author":"Baeken","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1471-4159.2009.06114.x","article-title":"Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity","volume":"110","author":"Hajieva","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1089\/ars.2011.4033","article-title":"Toxin models of mitochondrial dysfunction in Parkinson\u2019s disease","volume":"16","author":"Martinez","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00401-017-1794-7","article-title":"Neuronal complex I deficiency occurs throughout the Parkinson\u2019s disease brain, but is not associated with neurodegeneration or mitochondrial DNA damage","volume":"135","author":"Flones","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41531-023-00561-6","article-title":"Transient exposure to rotenone causes degeneration and progressive parkinsonian motor deficits, neuroinflammation, and synucleinopathy","volume":"9","author":"Webb","year":"2023","journal-title":"NPJ Park. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/mds.26513","article-title":"Dementia in Parkinson\u2019s disease is associated with enhanced mitochondrial complex I deficiency","volume":"31","author":"Gatt","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/bs.irn.2020.01.008","article-title":"The mitochondrial hypothesis: Dysfunction, bioenergetic defects, and the metabolic link to Alzheimer\u2019s disease","volume":"154","author":"Swerdlow","year":"2020","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The mechanisms of action of metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1126\/science.ade3332","article-title":"Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides","volume":"379","author":"Bridges","year":"2023","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1124\/jpet.104.068312","article-title":"Fenofibrate impairs rat mitochondrial function by inhibition of respiratory complex I","volume":"311","author":"Brunmair","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1741-7007-11-88","article-title":"Pioglitazone leads to an inactivation and disassembly of complex I of the mitochondrial respiratory chain","volume":"11","year":"2013","journal-title":"BMC Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2211933120","DOI":"10.1073\/pnas.2211933120","article-title":"Metformin acts in the gut and induces gut-liver crosstalk","volume":"120","author":"Tobar","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/path.4809","article-title":"The genetics and pathology of mitochondrial disease","volume":"241","author":"Alston","year":"2017","journal-title":"J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.mad.2011.03.002","article-title":"Differential cysteine depletion in respiratory chain complexes enables the distinction of longevity from aerobicity","volume":"132","author":"Schindeldecker","year":"2011","journal-title":"Mech. Ageing Dev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P","article-title":"Isolated complex I deficiency in children: Clinical, biochemical and genetic aspects","volume":"15","author":"Loeffen","year":"2000","journal-title":"Hum. Mutat."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e30952","DOI":"10.7554\/eLife.30952","article-title":"Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals","volume":"6","author":"Miranda","year":"2017","journal-title":"eLife"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41598-023-27689-y","article-title":"Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes","volume":"13","author":"Hozumi","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"132","article-title":"Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle","volume":"5","author":"Perrone","year":"2012","journal-title":"J. Nutr. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1007\/s11357-023-01059-y","article-title":"Mitochondrial complex I inhibition triggers NAD+-independent glucose oxidation via successive NADPH formation, \u201cfutile\u201d fatty acid cycling, and FADH2 oxidation","volume":"46","author":"Abrosimov","year":"2024","journal-title":"Geroscience"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s13679-019-00335-3","article-title":"Metformin: Mechanisms in Human Obesity and Weight Loss","volume":"8","author":"Yerevanian","year":"2019","journal-title":"Curr. Obes. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R728","DOI":"10.1152\/ajpregu.00837.2009","article-title":"Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states","volume":"299","author":"Hasek","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.exger.2012.07.005","article-title":"Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents","volume":"48","author":"Perrone","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s42003-022-04303-x","article-title":"OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases","volume":"6","author":"Sturm","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1222","DOI":"10.1038\/cddis.2014.166","article-title":"Transcriptional and metabolic adaptation of human neurons to the mitochondrial toxicant MPP(+)","volume":"5","author":"Krug","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.bbadis.2018.10.034","article-title":"Metabolomics of Ndufs4\u2212\/\u2212 skeletal muscle: Adaptive mechanisms converge at the ubiquinone-cycle","volume":"1865","author":"Terburgh","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115710","DOI":"10.1016\/j.celrep.2025.115710","article-title":"De novo serine biosynthesis is protective in mitochondrial disease","volume":"44","author":"Jackson","year":"2025","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.cmet.2016.01.019","article-title":"Mitochondrial DNA Replication Defects Disturb Cellular dNTP Pools and Remodel One-Carbon Metabolism","volume":"23","author":"Nikkanen","year":"2016","journal-title":"Cell Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e10575","DOI":"10.7554\/eLife.10575","article-title":"Mitochondrial dysfunction remodels one-carbon metabolism in human cells","volume":"5","author":"Bao","year":"2016","journal-title":"eLife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/s41467-022-28272-1","article-title":"Mitochondrial protein import determines lifespan through metabolic reprogramming and de novo serine biosynthesis","volume":"13","author":"Lionaki","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e13739","DOI":"10.1111\/acel.13739","article-title":"Cysteine restriction-specific effects of sulfur amino acid restriction on lipid metabolism","volume":"21","author":"Nichenametla","year":"2022","journal-title":"Aging Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1158\/2159-8290.CD-14-0250","article-title":"Serine catabolism regulates mitochondrial redox control during hypoxia","volume":"4","author":"Ye","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2016.08.009","article-title":"One-Carbon Metabolism in Health and Disease","volume":"25","author":"Ducker","year":"2017","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s10522-008-9130-1","article-title":"Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver","volume":"9","author":"Caro","year":"2008","journal-title":"Biogerontology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.exger.2013.02.021","article-title":"Regulation of longevity and oxidative stress by nutritional interventions: Role of methionine restriction","volume":"48","author":"Barja","year":"2013","journal-title":"Exp. Gerontol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.metabol.2009.10.023","article-title":"Methionine restriction effects on mitochondrial biogenesis and aerobic capacity in white adipose tissue, liver, and skeletal muscle of F344 rats","volume":"59","author":"Perrone","year":"2010","journal-title":"Metabolism"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.bbadis.2007.05.004","article-title":"Mitochondrial and cytosolic thiol redox state are not detectably altered in isolated human NADH: Ubiquinone oxidoreductase deficiency","volume":"1772","author":"Verkaart","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1186\/s12864-015-1883-8","article-title":"Transcriptome analysis of complex I-deficient patients reveals distinct expression programs for subunits and assembly factors of the oxidative phosphorylation system","volume":"16","author":"Szklarczyk","year":"2015","journal-title":"BMC Genom."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"101164","DOI":"10.1016\/j.redox.2019.101164","article-title":"Phenothiazine normalizes the NADH\/NAD+ ratio, maintains mitochondrial integrity and protects the nigrostriatal dopamine system in a chronic rotenone model of Parkinson\u2019s disease","volume":"24","author":"Tapias","year":"2019","journal-title":"Redox Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/j.bbabio.2017.09.005","article-title":"Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio","volume":"1858","author":"Anderson","year":"2017","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Nakao, K., Minato, N., and Uemoto, S. (2015). Diverting Glycolysis to Combat Oxidative Stress. Innovative Medicine, Springer.","DOI":"10.1007\/978-4-431-55651-0"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101609","DOI":"10.1016\/j.molmet.2022.101609","article-title":"Hepatic glycerol shunt and glycerol-3-phosphate phosphatase control liver metabolism and glucodetoxification under hyperglycemia","volume":"66","author":"Poursharifi","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/jbiol61","article-title":"Dynamic rerouting of the carbohydrate flux is key to counteracting oxidative stress","volume":"6","author":"Ralser","year":"2007","journal-title":"J. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"34316","DOI":"10.1074\/jbc.M505210200","article-title":"Magnesium and phosphate ions enable NAD binding to methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase","volume":"280","author":"Christensen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1000514","DOI":"10.1371\/journal.pbio.1000514","article-title":"Quiescent fibroblasts exhibit high metabolic activity","volume":"8","author":"Lemons","year":"2010","journal-title":"PLoS Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19611","DOI":"10.1073\/pnas.1117773108","article-title":"Hypoxia promotes isocitrate dehydrogenase-dependent carboxylation of \u03b1-ketoglutarate to citrate to support cell growth and viability","volume":"108","author":"Wise","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1042\/BST0330897","article-title":"The efficiency and plasticity of mitochondrial energy transduction","volume":"33 Pt 5","author":"Brand","year":"2005","journal-title":"Biochem. Soc. Trans."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.bbapap.2009.10.004","article-title":"The logic of the hepatic methionine metabolic cycle","volume":"1804","author":"Martinov","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.bbrc.2020.02.106","article-title":"Retrotransposon activation by distressed mitochondria in neurons","volume":"525","author":"Baeken","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1517\/13543784.11.10.1407","article-title":"Antioxidants as treatment for neurodegenerative disorders","volume":"11","author":"Moosmann","year":"2002","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e0177513","DOI":"10.1371\/journal.pone.0177513","article-title":"An integrative analysis of tissue-specific transcriptomic and metabolomic responses to short-term dietary methionine restriction in mice","volume":"12","author":"Ghosh","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.exger.2015.03.004","article-title":"Dietary L-methionine restriction decreases oxidative stress in porcine liver mitochondria","volume":"65","author":"Ying","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"165841","DOI":"10.1016\/j.bbadis.2020.165841","article-title":"Reprogramming of serine, glycine and one-carbon metabolism in cancer","volume":"1866","author":"Li","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.cmet.2020.02.017","article-title":"Serine Catabolism Feeds NADH when Respiration Is Impaired","volume":"31","author":"Yang","year":"2020","journal-title":"Cell Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1038\/s42255-021-00487-4","article-title":"Serine catabolism generates liver NADPH and supports hepatic lipogenesis","volume":"3","author":"Zhang","year":"2021","journal-title":"Nat. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.mad.2010.03.010","article-title":"Mitochondrial uncoupling and lifespan","volume":"131","author":"Mookerjee","year":"2010","journal-title":"Mech. Ageing Dev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s13105-025-01090-x","article-title":"Molecular mechanisms of UCP1-independent thermogenesis: The role of futile cycles in energy dissipation","volume":"81","author":"Sun","year":"2025","journal-title":"J. Physiol. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/414813a","article-title":"Biochemistry and molecular cell biology of diabetic complications","volume":"414","author":"Brownlee","year":"2001","journal-title":"Nature"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1007\/s00125-020-05275-5","article-title":"Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells","volume":"63","author":"Chareyron","year":"2020","journal-title":"Diabetologia"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"E430","DOI":"10.1073\/pnas.1514375113","article-title":"Identification of a mammalian glycerol-3-phosphate phosphatase: Role in metabolism and signaling in pancreatic \u03b2-cells and hepatocytes","volume":"113","author":"Mugabo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Schindeldecker, M., and Moosmann, B. (2024). Cysteine Is the Only Universally Affected and Disfavored Proteomic Amino Acid under Oxidative Conditions in Animals. Antioxidants, 13.","DOI":"10.3390\/antiox13030267"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/0003-9861(87)90531-5","article-title":"The inhibition site of MPP+, the neurotoxic bioactivation product of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine is near the Q-binding site of NADH dehydrogenase","volume":"259","author":"Ramsay","year":"1987","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11349\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T13:16:54Z","timestamp":1763990214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,24]]},"references-count":67,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311349"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311349","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,24]]}}}