Fig. 5
Fumarate accumulation is predominantly observed in Group 3 models. a 3D OrbiSIMS analysis of TCA metabolites after 16Ā h reveal low levels of malate (m/z 133.01), pyruvate (m/z 88.02), isocitrate (m/z 174.02) and glutamate (m/z 146.05), intermediate levels of Ī±-ketoglutarate (m/z 145.01), high levels of succinate (m/z 117.02) and very high levels of fumarate (m/z 115.00). b Normalised intensity measurements confirm the accumulation of succinate and fumarate and the concurrent lack of malate after 16Ā h in ONS-76 and HD-MB03 cells. c Gel supernatants of 3Ā week-old SHH (DAOY, ONS 76) and Group 3 (D458, HD MB03) nodules were collected 6, 24, 48 and 72Ā h after medium change to quantify the secretion levels of fumarate and malate. Note the increasingly higher fumarate levels in the group 3 nodules compared to SHH nodules over time. Malate levels were below the assay detection limit at all time points (mean; nā=ā3)