Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis. (8th June 2021)

• Record Type: Journal Article
• Authors: Shi, Chun; Guo, Han; Liu, Xintong
• Is Part Of: Cell transplantation. Volume 30(2021)
• Publication Date: 2021-06-08
• Subjects: mitochondrial transplantation -- platelet mitochondria -- hypoxia/reoxygenation -- FUN14 Domain Containing 2 -- neuronal apoptosis; Cell transplantation -- Periodicals; Cell Transplantation; Cell transplantation; Electronic journals; Periodicals; Periodicals; 571.638
• DOI: 10.1177/09636897211024210
• Languages: English
• ISSNs: 0963-6897

Abstract

Mitochondrial transplantation emerges as a novel therapeutic solution for ischemia/reperfusion injury (IRI) in various tissues. Platelets have recently been used in mitochondrial transplantation as readily-available donors of small-size platelet mitochondria (plt-mito). Interestingly, FUN14 Domain Containing 2 (FUNDC2), a protein highly-expressed in the outer membrane (OMM) of plt-mito, has been identified to maintain platelet survival under hypoxic condition. The current study determined whether and how FUNDC2 contributed to the therapeutic effect of plt-mito transplantation for hypoxia/reoxygenation (HR) injury. The results showed that incorporation of human plt-mito into SH-SY5Y cells rescued HR-induced mitochondrial malfunction and mitochondrial apoptotic pathway. Mechanistically, plt-mito transplantation led to an increased expression of FUNDC2 in the recipient cells. This protein induced mitochondrial translocation of phosphatidylinositol-3, 4, 5-trisphosphate (PIP3) via its N-term, resulting in the stimulation of the protein kinase B (Akt)/forkhead box O3a (FOXO3a) pathway, which inhibited HR-induced mitochondrial accumulation of a mitochondrial target of FOXO3a, Bim, also known as a pro-apoptotic protein. Therefore, the FUNDC2/PIP3/Akt/FOXO3a axis may facilitate the incorporated plt-mito to restore mitochondrial function and cell viability of the recipient cells, and platelets may serve as readily-available sources of donor mitochondria that afford therapeutic benefits against IRI.