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. 2019 Apr 18;4(8):e126749. doi: 10.1172/jci.insight.126749

Figure 5. Lysosomes are pivotal for PGC1α-dependent protection against cisplatin.

Figure 5

(A–D) Representative bright-field images (from n = 5/condition) of cisplatin-treated (10 μM, 24 hours) PGC1α Tg cells or vector controls TFEB siRNA knockdown (siCTRL or siTFEB, 50 μM, 72 hours). Scale bar: 1mm. (E) Viability via XTT assay in A–D. n = 6/condition. (F) Mitochondrial ROS (mtROS) via mitoSOX in (A–D). n = 6/condition. E and F analyzed by 2-way ANOVA. (G–J) Representative low- and high-power transmission electron microscopy (TEM, n = 3–5 mice/condition) of PGC1α-KO or WT proximal tubule 72 hours after cisplatin (20 mg/kg i.p.) showing swollen mitochondria (arrowheads). (K–N) Representative TEM of control or iNephPGC1α proximal tubule 72 hours after cisplatin (30 mg/kg i.p.) showing numerous electron-dense lysosomes (arrows), swollen mitochondria (arrowheads), and a swollen mitochondrion inside a membrane-bound structure consistent with mitophagy (plus sign). Scale bars: 2 μm (low power), 500 nm (high power). (O) Serum creatinine (Cr, mg/dl) in controls (n = 11) or iNephPGC1α (n = 12 mice) 72 hours after concurrent cisplatin (30 mg/kg i.p.) and chloroquine (10 mg/kg i.p.). (P and Q) Representative renal cortex staining (from n = 3–5 mice/condition) for 3-nitrotyrosine, a product of oxidative stress, in conditions indicated in (O). Scale bar: 200 μm. *P < 0.05 by Mann-Whitney U test.