Protective Role of the M-Sec–Tunneling Nanotube System in Podocytes

• DOI: 10.1681/asn.2020071076
• Publication Date: 2021-03-15T19:45:13Z
• Authors: 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 Durazzo; Hiroshi Ohno; Gabriella Gruden
• Keywords: Organelle

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