Cargando…

Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wu, Suhong, Zhang, Aijun, Li, Shumin, Chatterjee, Somik, Qi, Ruogu, Segura‐Ibarra, Victor, Ferrari, Mauro, Gupte, Anisha, Blanco, Elvin, Hamilton, Dale J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867055/
https://www.ncbi.nlm.nih.gov/pubmed/29593955
http://dx.doi.org/10.1002/advs.201700530
_version_ 1783308919478681600
author Wu, Suhong
Zhang, Aijun
Li, Shumin
Chatterjee, Somik
Qi, Ruogu
Segura‐Ibarra, Victor
Ferrari, Mauro
Gupte, Anisha
Blanco, Elvin
Hamilton, Dale J.
author_facet Wu, Suhong
Zhang, Aijun
Li, Shumin
Chatterjee, Somik
Qi, Ruogu
Segura‐Ibarra, Victor
Ferrari, Mauro
Gupte, Anisha
Blanco, Elvin
Hamilton, Dale J.
author_sort Wu, Suhong
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5867055
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-58670552018-03-28 Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration Wu, Suhong Zhang, Aijun Li, Shumin Chatterjee, Somik Qi, Ruogu Segura‐Ibarra, Victor Ferrari, Mauro Gupte, Anisha Blanco, Elvin Hamilton, Dale J. Adv Sci (Weinh) Full Papers 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. John Wiley and Sons Inc. 2018-01-03 /pmc/articles/PMC5867055/ /pubmed/29593955 http://dx.doi.org/10.1002/advs.201700530 Text en © 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Full Papers
Wu, Suhong
Zhang, Aijun
Li, Shumin
Chatterjee, Somik
Qi, Ruogu
Segura‐Ibarra, Victor
Ferrari, Mauro
Gupte, Anisha
Blanco, Elvin
Hamilton, Dale J.
Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title_full Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title_fullStr Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title_full_unstemmed Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title_short Polymer Functionalization of Isolated Mitochondria for Cellular Transplantation and Metabolic Phenotype Alteration
title_sort polymer functionalization of isolated mitochondria for cellular transplantation and metabolic phenotype alteration
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867055/
https://www.ncbi.nlm.nih.gov/pubmed/29593955
http://dx.doi.org/10.1002/advs.201700530
work_keys_str_mv AT wusuhong polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT zhangaijun polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT lishumin polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT chatterjeesomik polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT qiruogu polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT seguraibarravictor polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT ferrarimauro polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT gupteanisha polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT blancoelvin polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration
AT hamiltondalej polymerfunctionalizationofisolatedmitochondriaforcellulartransplantationandmetabolicphenotypealteration