Sex-related differences in SIRT3-mediated mitochondrial dynamics in renal ischemia/reperfusion injury

Transl Res. 2024 Mar 29;270:1-12. doi: 10.1016/j.trsl.2024.03.005. Online ahead of print.ABSTRACTThe prevalence of renal ischemia/reperfusion injury (IRI) in premenopausal women is considerably lower than that in age-matched men. This suggests that sex-related differences in mitochondrial function and homeostasis may contribute to sexual dimorphism in renal injury, though the mechanism remains unclear. Mouse model of unilateral left renal IRI with contralateral kidney enucleation, Ovariectomy in female mice, and a human embryonic kidney (HEK) cell model of hypoxia-reoxygenation were used to study how estrogen affects the sexual dimorphism of renal IRI through SIRT3 in vitro and in vivo, respectively. Here, we demonstrate differential expression of renal SIRT3 may induce sexual dimorphism in IRI using the renal IRI model. Higher SIRT3 level in female mice was associated with E2-induced protection of renal tubular epithelium, reduced mitochondrial reactive oxygen species (ROS), and IRI resistance. In hypoxia-reoxygenated HEK cells, SIRT3 knockdown increased oxidative stress, shifted the interconnected mitochondrial network toward fission, exacerbated hypoxia/reoxygenation-induced endoplasmic reticulum stress (ERS), and abolished the protective effects of E2 on IRI. Mechanistically, the SIRT3 level is E2-dependent and that E2 increases the SIRT3 protein level via estrogen receptor. SIRT3 targeted an i-AAA protease, yeast mitochondrial AAA metalloprotease (YME1L1), and hydrolyzed...
Source: Translational Research : the journal of laboratory and clinical medicine - Category: Laboratory Medicine Authors: Source Type: research