New Publication: Exploring Mitochondrial Dysfunction in Kidney Disease

I am pleased to share the publication of a new research article to which I contributed as second author, recently published in the Journal of the American Society of Nephrology (JASN): “CLUH Inhibition by Lipocalin-2 Orchestrates Mitochondrial Disruption and Contributes to Kidney Disease.”

This work was conducted at the INEM – Institut Necker Enfants Malades and represents a collaborative effort aimed at better understanding the molecular mechanisms linking kidney injury to mitochondrial dysfunction and chronic kidney disease progression.

Summary of the study

Lipocalin-2 (LCN2) is a secreted protein involved in transporting hydrophobic molecules, regulating antibacterial responses and iron homeostasis. LCN2 expression increases following kidney damage, and participates to chronic kidney disease (CKD) onset. We previously identified LCN2 as a regulator of mitochondrial dysfunction in renal tubular cells. this study aims to better understand LCN2 role in mitochondrial dysfunction and kidney pathology.

In this study, we investigated the role of Lipocalin-2 (LCN2), a protein known to be strongly induced following kidney injury and associated with chronic kidney disease. We identified CLUH (Clustered Mitochondrial Homolog) as a key molecular partner of LCN2. CLUH is a central regulator of mitochondrial homeostasis, controlling the translation of nuclear-encoded mitochondrial proteins.

Our results show that increased LCN2 levels inhibit CLUH activity, leading to abnormal mitochondrial organization, impaired mitochondrial function, and ultimately contributing to kidney fibrosis and loss of renal function. Importantly, CLUH expression was found to be reduced in both experimental models of kidney disease and in human patients, where it inversely correlated with disease severity.

Why this matters

These findings uncover a previously unrecognized mechanism linking inflammation-associated proteins to mitochondrial dysfunction in kidney disease. By identifying the LCN2–CLUH axis as a driver of mitochondrial disruption, this work opens new perspectives for therapeutic strategies aimed at preserving mitochondrial function to slow chronic kidney disease progression.

Reference

CLUH Inhibition by Lipocalin-2 Orchestrates Mitochondrial Disruption and Contributes to Kidney Disease

Marques E, Teixeira MA, Parra CR, Isnard P, Kelly-Aubert M, Nguyen C, Lake J, Nemazanyy I, Rugarli EI, Terzi F, Gallazzini M.

Journal of the American Society of Nephrology (Dec 2025). doi: 10.1681/ASN.0000000961