Fig. 7: Oenocyte-specific Pex5 activation alleviates age-related PIS and preserves cardiac function.

a QRT-PCR analysis showing expression of Pex5 in oenocytes dissected from flies with oenocyte-specific overexpression of Pex5. N = 3 biological samples from 2 independent experiments. b QRT-PCR analysis showing relative mRNA expression of upd3 in 4-week-old oenocytes dissected from flies with oenocyte-specific overexpression of Pex5. N = 4 independent biological samples. c Representative images to show co-localization of anti-Pmp70 and anti-SKL immunostaining in 6-week-old oenocytes dissected from flies with oenocyte-specific overexpression of Pex5 (yellow dots). Scale bar: 6.7 µm. d Quantification of SKL-positive punctae in c. Quantification of the percentage of peroxisomal ghosts (Pmp70-punctae with no SKL signals) per region of interest (166.41 µm2) in c. f Quantification of Pmp70-positive punctae in c. d–f. Dot plot shows the quantifications of 6 biological replicates, 6 ROIs per replicate. g Representative M-mode of flies with oenocyte-specific Pex5 overexpression under paraquat treatment. h Arrhythmia index of flies with oenocyte-specific Pex5 overexpression under paraquat treatment. (nleft-right = 15,14,14,21 flies). iRepresentative M-mode of flies with oenocyte-specific Pex5 overexpression during normal aging. j Arrhythmia index of flies with oenocyte-specific Pex5 overexpression (red dots) during normal aging (2-week, 4-week and 6-week-old), n0RU,y-o = 35, 15, 15 flies; n200RU,y-o = 9, 15, 18 flies. k DHE staining in 6-week-old oenocytes from flies with oenocyte-specific overexpression of Pex5. Scale bar: 20 µm. l Quantification of the percentage of DHE-positive staining in k. N = 6 flies, 3 ROIs per replicate. Ctrl genotype is PromEGS>Pex5OE with no RU feeding. Data are represented as mean ± SEM. P values are calculated using two-sided unpaired t-test (a, b, d–f, l, j) or two-way ANOVA, followed by Holm-sidak multiple comparisons (h). m Proposed model to show that impaired hepatic peroxisomal import promotes ROS production, JNK activation, and peroxikine upd3 expression, which non-autonomously controls cardiac JAK-STAT and arrhythmia. Overexpression of endogenous Pex5 preserves cardiac health.