Protective role of the M-sec-tunneling nanotube system in podocytes

Federica Barutta, Shunsuke Kimura, Koji Hase, Stefania Bellini, Beatrice Corbetta, Alessandro Corbelli, Fabio Fiordaliso, Antonella Barreca, Mauro Giulio Papotti, Gian Marco Ghiggeri, Gennaro Salvidio, Dario Roccatello, Valentina Audrito, Silvia Deaglio, Roberto Gambino, Stefania Bruno, Giovanni Camussi, Miriam Martini, Emilio Hirsch, Marilena DurazzoHiroshi Ohno, Gabriella Gruden

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background Podocyte dysfunction and loss are major determinants in the development of proteinuria. FSGS is one of the most common causes of proteinuria, but the mechanisms leading to podocyte injury or conferring protection against FSGS remain poorly understood. The cytosolic protein M-Sec has been involved in the formation of tunneling nanotubes (TNTs), membrane channels that transiently connect cells and allow intercellular organelle transfer. Whether podocytes express M-Sec is unknown and the potential relevance of the M-Sec-TNT system in FSGS has not been explored. Methods We studied the role of the M-Sec-TNT system in cultured podocytes exposed to Adriamycin and in BALB/c M-Sec knockout mice. We also assessed M-Sec expression in both kidney biopsies from patients with FSGS and in experimental FSGS (Adriamycin-induced nephropathy). Results Podocytes can form TNTs in a M-Sec-dependent manner. Consistent with the notion that the M-Sec-TNT system is cytoprotective, podocytes overexpressed M-Sec in both human and experimental FSGS. Moreover, M-Sec deletion resulted in podocyte injury, with mitochondrial abnormalities and development of progressive FSGS. In vitro, M-Sec deletion abolished TNT-mediated mitochondria transfer between podocytes and altered mitochondrial bioenergetics. Re-expression of M-Sec reestablishes TNT formation and mitochondria exchange, rescued mitochondrial function, and partially reverted podocyte injury. Conclusions These findings indicate that the M-Sec-TNT system plays an important protective role in the glomeruli by rescuing podocytes via mitochondrial horizontal transfer. M-Sec may represent a promising therapeutic target in FSGS, and evidence that podocytes can be rescued via TNT-mediated horizontal transfer may open new avenues of research.

Original languageEnglish
Pages (from-to)1114-1130
Number of pages17
JournalJournal of the American Society of Nephrology
Issue number5
Publication statusPublished - 2021 May

ASJC Scopus subject areas

  • General Medicine


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