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NDUFS4 regulates cristae remodeling in diabetic kidney disease

Author

Listed:
  • Koki Mise

    (The University of Texas MD Anderson Cancer Center
    Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences)

  • Jianyin Long

    (The University of Texas MD Anderson Cancer Center)

  • Daniel L. Galvan

    (The University of Texas MD Anderson Cancer Center)

  • Zengchun Ye

    (The Third Affiliated Hospital of Sun Yat-Sen University)

  • Guizhen Fan

    (The University of Texas Health Science Center at Houston)

  • Rajesh Sharma

    (The University of Texas Health Science Center at Houston)

  • Irina I. Serysheva

    (The University of Texas Health Science Center at Houston)

  • Travis I. Moore

    (The University of Texas Health Science Center at Houston)

  • Collene R. Jeter

    (The University of Texas MD Anderson Cancer Center)

  • M. Anna Zal

    (The University of Texas MD Anderson Cancer Center)

  • Motoo Araki

    (Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences)

  • Jun Wada

    (Rheumatology, Endocrinology & Metabolism, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences)

  • Paul T. Schumacker

    (Feinberg School of Medicine, Northwestern University)

  • Benny H. Chang

    (The University of Texas MD Anderson Cancer Center)

  • Farhad R. Danesh

    (The University of Texas MD Anderson Cancer Center
    Baylor College of Medicine)

Abstract

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.

Suggested Citation

  • Koki Mise & Jianyin Long & Daniel L. Galvan & Zengchun Ye & Guizhen Fan & Rajesh Sharma & Irina I. Serysheva & Travis I. Moore & Collene R. Jeter & M. Anna Zal & Motoo Araki & Jun Wada & Paul T. Schum, 2024. "NDUFS4 regulates cristae remodeling in diabetic kidney disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46366-w
    DOI: 10.1038/s41467-024-46366-w
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