Open AccessPolymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
Author(s) -
Wu Suhong,
Zhang Aijun,
Li Shumin,
Chatterjee Somik,
Qi Ruogu,
SeguraIbarra Victor,
Ferrari Mauro,
Gupte Anisha,
Blanco Elvin,
Hamilton Dale J.
Publication year - 2018
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201700530
Subject(s) - mitochondrion , transplantation , microbiology and biotechnology , oxidative phosphorylation , mitophagy , internalization , chemistry , biology , biochemistry , cell , medicine , autophagy , apoptosis , surgery
Aberrant mitochondrial energy transfer underlies prevalent chronic health conditions, including cancer, cardiovascular, and neurodegenerative diseases. Mitochondrial transplantation represents an innovative strategy aimed at restoring favorable metabolic phenotypes in cells with dysfunctional energy metabolism. While promising, significant barriers to in vivo translation of this approach abound, including limited cellular uptake and recognition of mitochondria as foreign. The objective is to functionalize isolated mitochondria with a biocompatible polymer to enhance cellular transplantation and eventual in vivo applications. Herein, it is demonstrated that grafting of a polymer conjugate composed of dextran with triphenylphosphonium onto isolated mitochondria protects the organelles and facilitates cellular internalization compared with uncoated mitochondria. Importantly, mitochondrial transplantation into cancer and cardiovascular cells has profound effects on respiration, mediating a shift toward improved oxidative phosphorylation, and reduced glycolysis. These findings represent the first demonstration of polymer functionalization of isolated mitochondria, highlighting a viable strategy for enabling clinical applications of mitochondrial transplantation.