Extended Data Fig. 4: Related to HK detachment from the OMM promotes aerobic glycolysis.
(a) Specific growth rates for control cells (mean ± s.d., n = 3 biologically independent samples). Two-tailed Welch’s t-test. (b) Flow cytometric analysis of HK2-knockout and control cells stained with 7-Aminoactinomycin D (7-AAD), which is excluded from live cells. (c) Relative growth rates for HK2-knockout versus control cells (mean ± s.d., n = 3 biologically independent samples). Two-tailed Welch’s t-test comparing the respective mean ± s.d. (bar) versus mean ± s.d. (control cells) between bars. (d) Net rates of lactate secretion versus glucose uptake in HK2-knockout cells (mean ± s.e.m., n = 3 biologically independent samples). Two-tailed Welch’s t-test. (e, f, g, h, j) Fractional labeling of pyruvate (e, f), serine (g), citrate (h), and malate (j) in HK2-knockout cells (mean ± s.d., n = 3 biologically independent samples) grown in conditions with [U-13C-glucose]. Defined lactate levels in HPLM and RPMI (f, bottom right). (i, k) Total 13C labeling of citrate (i) and malate (k) in HK2-knockout cells (mean ± s.d., n = 3 biologically independent samples) grown in conditions with [U-13C-glucose]. (l) Schematic depicting the incorporation of 13C from [1,2-13C] glucose into 3-phosphoglycerate (3PG) and lactate. Orange-outlined box, labeling generated when [1,2-13C] glucose is metabolized via the oxidative pentose phosphate pathway (ox-PPP). Green-outlined box, labeling generated when [1,2-13C] glucose is metabolized via glycolysis. (m, n) Fractional labeling of 3PG (m) and lactate (n) in HK2-knockout cells (mean ± s.d., n = 3 biologically independent samples) grown in conditions with [1,2-13C-glucose]. In e, f, g, h, i, j, k, m, and n, Values above brackets indicate differences in fractional labeling between bars. Two-tailed Welch’s t-test.
