Mitofusin2 expression is associated with podocyte injury in IgA nephropathy

BACKGROUND: Podocyte injury is associated with IgA nephropathy (IgAN) prognosis. Mitochondrial dysfunction is a major contributor to podocyte injury and death. Mitofusin2 (Mfn2) plays an important role in regulating the morphology and function of mitochondria. This study aimed to investigate the potential of Mfn2 as a biomarker to evaluate the degree of podocyte injury. METHODS: This single-center, retrospective study enrolled 114 patients with biopsy-proven IgAN. Immunofluorescence and TUNEL staining were applied, and clinical and pathological features were compared between patients with different patterns of Mfn2 expression. RESULTS: In IgAN, Mfn2 is mainly expressed in podocytes and significantly associated with nephrin, TUNEL, and Parkin staining. Among the 114 IgAN patients, 28 (24.56%) did not exhibit Mfn2 expression in podocytes. The patients in the Mfn2-negative group had lower serum albumin (34.43 ± 4.64 g/L vs. 36.48 ± 3 .52 g/L, P = 0.015) and estimated glomerular filtration rate (eGFR) (76.59 ± 35.38 mL/min vs. 92.13 ± 25.35 mL/min, P = 0.013), higher 24 h proteinuria (2.48 ± 2.72 g/d vs. 1.27 ± 1.31 g/d, P = 0.002), serum creatinine (Scr) (107.39 ± 57.97 μmol/L vs. 84.70 ± 34.95 μmol/L, P = 0.015), blood urea nitrogen (BUN) (7.36 ± 4.45 mmol/L vs. 5.68 ± 2.14 mmol/L, P = 0.008), and higher S/T scores (92.86% vs. 70.93% and 42.85% vs. 15.12%, respectively, P < 0.05). In the Mfn2-negative group, the mitochondria were punctate and round ridges disappeared, and a lower length-to-width ratio and much higher M/A ratio were observed. Correlation analysis showed that the intensity of Mfn2 was negatively correlated with Scr (r = − 0.232, P = 0.013), 24 h proteinuria (r = − 0.541, P = 0.001), and the degree of podocyte effacement (r = − 0.323, P = 0.001), and positively correlated with eGFR (r = 0.213, P = 0.025). Logistic regression analysis showed that the Mfn2-negative group had a higher risk of severe podocyte effacement (≥ 50%) (OR = 3.061, P = 0.019). CONCLUSION: Mfn2 was negatively correlated with proteinuria and renal function. A lack of Mfn2 in podocytes indicates severe podocyte injury and a high degree of podocyte effacement.