ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: PO2442

Loss of Macrophage Mitofusin 2 but Not Mitofusin 1 Suppresses Mitochondrial Biogenesis and Promotes Kidney Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms


  • Bhatia, Divya, Weill Cornell Medicine, New York, New York, United States
  • Capili, Allyson M., Weill Cornell Medicine, New York, New York, United States
  • Nakahira, Kiichi, Weill Cornell Medicine, New York, New York, United States
  • Muthukumar, Thangamani, Weill Cornell Medicine, New York, New York, United States
  • Choi, Augustine MK, Weill Cornell Medicine, New York, New York, United States
  • Choi, Mary E., Weill Cornell Medicine, New York, New York, United States

Mitochondrial biogenesis, dynamics (fusion/fission) and mitophagy exert critical roles in maintaining mitochondrial function and protect against oxidative stress. Macrophages are well-known to aggravate kidney injury-induced inflammation and fibrosis in the pathogenesis of chronic kidney disease (CKD). We studied the effects of macrophage mitofusins: Mfn1 and/or Mfn2 deficiency on mitochondrial biogenesis during CKD.


Myeloid-specific Mfn1 (Mfn1fl/fl,LysM-Cre+/-), Mfn2 (Mfn2fl/fl,LysM-Cre+/-), & double knockout (DKO) mice and corresponding controls were fed with control (Ctl) or adenine diet (AD) for 28-days. Kidneys,kidney macrophages,bone marrow-derived macrophages (BMDM) were analyzed by western blot,flow cytometry, immunohistochemistry. Blood urea nitrogen (BUN),creatinine were measured.


Expression of mitochondrial biogenesis regulator: PGC-1α, antioxidant enzyme: superoxide dismutase-2, mitochondrial fusion proteins: Mfn1, Mfn2, and OPA-1 decreased while fission proteins: DRP-1 and phospo-DRP-1-Serine-616 increased in the kidneys after AD and BMDM after TGF-β1 treatment. Kidney macrophage superoxide levels increased after AD.However, kidney macrophages from AD-fed Mfn2fl/fl,LysM-Cre+/- and DKO mice but not Mfn1fl/fl,LysM-Cre+/- mice displayed higher superoxide & increased expression of galectin-3, TGF-β1, & CD206 than corresponding controls. In addition, Mfn2fl/fl,LysM-Cre+/- and DKO mice displayed greater collagen accumulation, and increased BUN and creatinine after AD than wild-type and Mfn1fl/fl,LysM-Cre+/- mice. Wild-type and Mfn1fl/fl,LysM-Cre+/- mice showed similar increases in collagen deposition in the kidney and worsening of kidney function after AD. BMDM from Mfn1fl/fl,LysM-Cre+/- and wild-type mice also showed similar expression of profibrotic macrophage marker, arginase-I after TGF-β1-treatment. However, TGF-β1-treated Mfn2fl/fl,LysM-Cre+/- and DKO BMDM and kidney macrophages displayed greater polarization towards profibrotic phenotype while lower expression of PGC-1α and defective mitophagy than Mfn1fl/fl,LysM-Cre+/- and wild-type macrophages.


Macrophage-specific deficiency of Mfn2 but not Mfn1 causes impairments in mitochondrial biogenesis and mitophagy, thereby promoting polarization towards profibrotic macrophage phenotype and kidney fibrosis.


  • Other NIH Support