Fig. 3: Sex differences in mitochondrial respiration and energy precursor metabolism of proximal tubular cells. | Nature Communications

Fig. 3: Sex differences in mitochondrial respiration and energy precursor metabolism of proximal tubular cells.

From: Single-cell profiling of healthy human kidney reveals features of sex-based transcriptional programs and tissue-specific immunity

Fig. 3

a Depiction of selected significant (FDR < 0.25) terms identified by GSEA analysis as being enriched in males and females, respectively. Source data are provided in Supplementary Data 3. P values were calculated by Wilcoxon rank sum test without multiple comparison adjustment. b Oxygen consumption rate (OCR) was monitored to assess the mitochondrial respiration of male and female PT cells at baseline and after metabolic stress (n = 3 donors/sex; n = 21 replicates/male sex, and 23 replicates/female sex). To induce metabolic stress, the following sequence of drugs was injected: 1 μM oligomycin, 0.3 μM FCCP, 100 mM 2-DG, 1 mM Rot/AA. The OCR was monitored in male and female PT cells (n = 3 donors/sex; n = 21 replicates/male sex, and 23 replicates/female sex). Data are presented as mean values + /- SEM. c The basal OCR (p < 0.0001, u = 48), ATP-linked respiration (p < 0.0001, t = 5.223, df=42), reserve capacity (p < 0.0001, t = 5.018, df=42) and maximal respiratory capacity (p < 0.0001, t = 5.281, df=42) of male and female PT cells were calculated from the OCR curves in b. Group-to-group differences were assessed using two-tailed unpaired T tests for variables following a normal distribution (ATP-linked respiration, reserve capacity, maximal respiratory capacity), and Mann-Whitney tests for variables with a non-parametric distribution (Basal respiration). Data are presented as mean values + /- SEM. d In a separate experiment, the intracellular levels of ATP (p < 0.0001, t = 5.959, df=34), NAD (p = 0.029, u = 93), β-nicotinamide mononucleotide (p < 0.0001, t = 4.575, df=34), GTP (p < 0.0001, t = 7.45, df=34), ITP (p = 0.0001, u = 46), and UTP (p = 0.0001, t = 4.316, df=34) were determined in male and female PT cells (n = 3 donors/sex; n = 6 replicates/donor). Data are presented as mean values + /- SEM. Source data for (b–d) are provided as a source data file. Group-to-group differences were assessed using two-tailed unpaired T tests for variables following a normal distribution (ATP, β-nicotinamide, GTP, UTP), and Mann-Whitney tests for variables with a non-parametric distribution (NAD, ITP). *p < 0.05;**p < 0.01;***p < 0.001;****p < 0.0001. PT proximal tubule, AUC area under the curve, OCR oxygen consumption rate, FCCP p-trifluoromethoxy carbonyl cyanide phenyl hydrazone, 2-DG 2-deoxyglucose, Rot rotenone, AA antimycin A, df degrees of freedom. Orange = males, dark purple = females. Circle, square, and triangle symbols indicate biologically independent donors for each sex.

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