{
"METABOLOMICS WORKBENCH":{"STUDY_ID":"ST002542","ANALYSIS_ID":"AN004188","VERSION":"1","CREATED_ON":"10-30-2024"},

"PROJECT":{"PROJECT_TITLE":"The metabolomics analysis of Methionine restriction","PROJECT_TYPE":"targeted metabolomics data","PROJECT_SUMMARY":"Methionine restriction (MR) provides metabolic benefits in many organisms. However, mechanisms underlying the MR-induced effect remain incompletely understood. Here, we show in the budding yeast S. cerevisiae that MR relays a signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic mitochondria to nitrogenic anabolism.In particular, decreases in cellular SAM constrain lipoate metabolism and protein lipoylation required for the operation of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete glucose oxidation with an exit of acetyl-CoA and alpha-ketoglutarate from the TCA cycle to the syntheses of amino acids, such as arginine and leucine. This mitochondrial SAM-induced response, namely mitoSIR, promotes cell fitness through the coordination of mitochondrial fuel metabolism with the nitrogenic synthesis of amino acids.","INSTITUTE":"Zhejiang University","DEPARTMENT":"Life Sciences Institute","LAST_NAME":"Cunqi","FIRST_NAME":"Ye","ADDRESS":"866 Yuhangtang Rd, Hangzhou 310058, P.R. China","EMAIL":"yecunqi@zju.edu.cn","PHONE":"15267181160","DOI":"http://dx.doi.org/10.21228/M83M7P"},

"STUDY":{"STUDY_TITLE":"Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids (Part 2)","STUDY_SUMMARY":"Methionine restriction (MR) provides metabolic benefits in many organisms. However, mechanisms underlying the MR-induced effect remain incompletely understood. Here, we show in the budding yeast S. cerevisiae that MR relays a signal of S-adenosylmethionine (SAM) deprivation to adapt bioenergetic mitochondria to nitrogenic anabolism. In particular, decreases in cellular SAM constrain lipoate metabolism and protein lipoylation required for the operation of the tricarboxylic acid (TCA) cycle in the mitochondria, leading to incomplete glucose oxidation with an exit of acetyl-CoA and alpha-ketoglutarate from the TCA cycle to the syntheses of amino acids, such as arginine and leucine. This mitochondrial SAM-induced response, namely mitoSIR, promotes cell fitness through the coordination of mitochondrial fuel metabolism with the nitrogenic synthesis of amino acids.","INSTITUTE":"ZheJiang University","DEPARTMENT":"Life Sciences Institute","LAST_NAME":"Cunqi","FIRST_NAME":"Ye","ADDRESS":"866 Yuhangtang Rd, Hangzhou 310058, P.R. China","EMAIL":"yecunqi@zju.edu.cn","PHONE":"15267181160","SUBMIT_DATE":"2023-04-05"},

"SUBJECT":{"SUBJECT_TYPE":"Yeast","SUBJECT_SPECIES":"Saccharomyces cerevisiae","TAXONOMY_ID":"4932","GENOTYPE_STRAIN":"CEN.P.K"},
"SUBJECT_SAMPLE_FACTORS":[
{
"Subject ID":"-",
"Sample ID":"S1S2 0h_1",
"Factors":{"label":"0h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 0h_1"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 0h_2",
"Factors":{"label":"0h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 0h_2"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 0h _3",
"Factors":{"label":"0h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 0h _3"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_1",
"Factors":{"label":"15h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_1"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_2",
"Factors":{"label":"15h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_2"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_3",
"Factors":{"label":"15h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_3"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_1+",
"Factors":{"label":"15h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_1+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_2+",
"Factors":{"label":"15h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_2+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 15h_3+",
"Factors":{"label":"15h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 15h_3+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_1",
"Factors":{"label":"2h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_1"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_2",
"Factors":{"label":"2h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_2"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_3",
"Factors":{"label":"2h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_3"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_1+",
"Factors":{"label":"2h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_1+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_2+",
"Factors":{"label":"2h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_2+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 2h_3+",
"Factors":{"label":"2h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 2h_3+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_1",
"Factors":{"label":"4h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_1"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_2",
"Factors":{"label":"4h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_2"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_3",
"Factors":{"label":"4h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_3"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_1+",
"Factors":{"label":"4h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_1+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_2+",
"Factors":{"label":"4h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_2+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 4h_3+",
"Factors":{"label":"4h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 4h_3+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_1",
"Factors":{"label":"6h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_1"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_2",
"Factors":{"label":"6h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_2"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_3",
"Factors":{"label":"6h"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_3"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_1+",
"Factors":{"label":"6h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_1+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_2+",
"Factors":{"label":"6h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_2+"}
},
{
"Subject ID":"-",
"Sample ID":"S1S2 6h_3+",
"Factors":{"label":"6h+"},
"Additional sample data":{"RAW_FILE_NAME":"S1S2 6h_3+"}
}
],
"COLLECTION":{"COLLECTION_SUMMARY":"Care was taken to quench cells quickly in -40℃ and maintain metabolites in acid to minimize oxidation","SAMPLE_TYPE":"Yeast cells"},

"TREATMENT":{"TREATMENT_SUMMARY":"Mutant SAM1SAM2 DKO cells were cultured in SD medium with the supplements of SAM and growed to log phase, then cells were washed with normal SD medium and re-cultured in SD medium"},

"SAMPLEPREP":{"SAMPLEPREP_SUMMARY":"Briefly, equal OD units of cells were rapidly quenched to stop metabolism by addition into 4 volumes of quenching buffer containing 60% methanol and 10 mM Tricine, pH 7.4 that was pre-cooled to -40°C. 5 min after holding at -40°C, cells were spun at 5,000 g for 3 min at 0°C, washed with the same buffer, and then resuspended in 1 mL extraction buffer containing 75% ethanol and 0.5 mM Tricine, pH 7.4. Intracellular metabolites were extracted by incubating at 75°C for 3 min, followed by chilling on ice for 5 min. Samples were spun at 20,000 g for 1 min to pellet cell debris, and 0.9 mL of the supernatant was transferred to a new tube. After a second spin at 20,000 g for 10 min, 0.8 mL of the supernatant was transferred to a new tube. Metabolites in the extraction buffer were dried using a vacuum concentrator system (Labconco) and stored at -80°C until analysis. Dried metabolite extracts were resuspended in 60% acetonitrile for injection."},

"CHROMATOGRAPHY":{"INSTRUMENT_NAME":"Shimadzu 20AD","COLUMN_NAME":"Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um)","COLUMN_TEMPERATURE":"45","FLOW_GRADIENT":"0.01 min 80% B, 20 min 20% B, 20.5 min 80% B, 34 min 80% B.","FLOW_RATE":"0.15ml/min","SOLVENT_A":"20 mM ammonium carbonate and 0.1% (v/v) ammonium hydroxide","SOLVENT_B":"acetonitrile","CHROMATOGRAPHY_TYPE":"HILIC"},

"ANALYSIS":{"ANALYSIS_TYPE":"MS"},

"MS":{"INSTRUMENT_NAME":"ABI Sciex 6500+ QTrap","INSTRUMENT_TYPE":"Triple quadrupole","MS_TYPE":"ESI","MS_COMMENTS":"SCIEX OS","ION_MODE":"POSITIVE"},

"MS_METABOLITE_DATA":{
"Units":"Peak intensity",

"Data":[{"Metabolite":"13C-Alanine-1","S1S2 0h_1":"","S1S2 0h_2":"","S1S2 0h _3":"","S1S2 15h_1":"","S1S2 15h_2":"","S1S2 15h_3":"","S1S2 15h_1+":"","S1S2 15h_2+":"","S1S2 15h_3+":"","S1S2 2h_1":"","S1S2 2h_2":"","S1S2 2h_3":"","S1S2 2h_1+":"","S1S2 2h_2+":"","S1S2 2h_3+":"","S1S2 4h_1":"","S1S2 4h_2":"","S1S2 4h_3":"","S1S2 4h_1+":"","S1S2 4h_2+":"","S1S2 4h_3+":"","S1S2 6h_1":"","S1S2 6h_2":"","S1S2 6h_3":"","S1S2 6h_1+":"","S1S2 6h_2+":"","S1S2 6h_3+":""},{"Metabolite":"13C-Arginine-1","S1S2 0h_1":"2932.9005","S1S2 0h_2":"4779.5979","S1S2 0h _3":"5983.2110","S1S2 15h_1":"72596.3944","S1S2 15h_2":"25726.5272","S1S2 15h_3":"31540.6617","S1S2 15h_1+":"114455.8032","S1S2 15h_2+":"100973.0646","S1S2 15h_3+":"31808.1741","S1S2 2h_1":"6121.9273","S1S2 2h_2":"8895.0311","S1S2 2h_3":"5163.1819","S1S2 2h_1+":"42824.6592","S1S2 2h_2+":"8927.6346","S1S2 2h_3+":"14657.3494","S1S2 4h_1":"5257.8519","S1S2 4h_2":"8867.6083","S1S2 4h_3":"14203.2118","S1S2 4h_1+":"19428.5564","S1S2 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6h_1+":"","S1S2 6h_2+":"","S1S2 6h_3+":""},{"Metabolite":"13C lysine","S1S2 0h_1":"","S1S2 0h_2":"2870.2260","S1S2 0h _3":"","S1S2 15h_1":"","S1S2 15h_2":"","S1S2 15h_3":"","S1S2 15h_1+":"1674.2772","S1S2 15h_2+":"","S1S2 15h_3+":"","S1S2 2h_1":"","S1S2 2h_2":"","S1S2 2h_3":"","S1S2 2h_1+":"","S1S2 2h_2+":"2152.6739","S1S2 2h_3+":"","S1S2 4h_1":"","S1S2 4h_2":"","S1S2 4h_3":"","S1S2 4h_1+":"","S1S2 4h_2+":"","S1S2 4h_3+":"","S1S2 6h_1":"","S1S2 6h_2":"","S1S2 6h_3":"","S1S2 6h_1+":"","S1S2 6h_2+":"","S1S2 6h_3+":""},{"Metabolite":"13C-Lysine-1","S1S2 0h_1":"1224346.6390","S1S2 0h_2":"","S1S2 0h _3":"849673.1753","S1S2 15h_1":"346699.9941","S1S2 15h_2":"721181.5093","S1S2 15h_3":"303027.4937","S1S2 15h_1+":"298014.6576","S1S2 15h_2+":"672949.6686","S1S2 15h_3+":"533855.2842","S1S2 2h_1":"545264.9008","S1S2 2h_2":"1166916.9600","S1S2 2h_3":"676793.3056","S1S2 2h_1+":"1071659.3780","S1S2 2h_2+":"1176751.1410","S1S2 2h_3+":"812105.8531","S1S2 4h_1":"","S1S2 4h_2":"767537.7058","S1S2 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