Review Article Open Access
Volume 3 | Issue 6 | DOI: https://doi.org/10.33696/immunology.3.118

Megalin-Mediated Trafficking of Mitochondrial Intracrines: Relevance to Signaling and Metabolism

  • 1Division of Nephrology and Selzman Institute for Kidney Health, Department of Medicine, Baylor College of Medicine, Houston,Texas, 77030 USA
  • 2Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. Debakey VAMC, Houston, Texas, 77030 USA
+ Affiliations - Affiliations

Corresponding Author

David Sheikh-Hamad, sheikh@bcm.tmc.edu

Received Date: July 13, 2021

Accepted Date: November 23, 2021


The multi-ligand binding protein megalin (LRP2) is ubiquitously expressed and facilitates cell uptake of hormones, nutrients and vitamins. We have recently shown megalin is present in the mitochondria of cultured epithelial and mesenchymal cells, as well as many organs and tissues. Mitochondrial megalin associates with stanniocalcin-1 and SIRT3; two proteins that promote anti-oxidant defenses. Megalin shuttles mitochondrial intracrines (angiotensin II, stanniocalcin-1 and TGF-ß) from the cell surface to the mitochondria through the retrograde early endosome to Golgi pathway and requires Rab32. Deletion of megalin impairs mitochondrial respiration and glycolysis. This pathway overlaps molecular and vesicular trafficking defects common to Donai Barrow and Lowe syndromes, suggesting that mitochondrial intracrine signaling defects may contribute to the pathogenesis of these diseases.


Proteinuria, ApoE, Vitamin D, Cubulin, OCRL1, PIKfyve, Donnai Barrow and Lowe syndromes

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