Mitochondrial Transplantation: the Advance to Therapeutic Application and Molecular Modulation

Overview

Journal Front Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2024 Jan 1

PMID 38162128

Authors

James D McCully

Pedro J Del Nido

Sitaram M Emani

Affiliations

Soon will be listed here.

Abstract

Mitochondrial transplantation provides a novel methodology for rescue of cell viability and cell function following ischemia-reperfusion injury and applications for other pathologies are expanding. In this review we present our methods and acquired data and evidence accumulated to support the use of mitochondrial transplantation.

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References

Moskowitzova K, Orfany A, Liu K, Ramirez-Barbieri G, Thedsanamoorthy J, Yao R . Mitochondrial transplantation enhances murine lung viability and recovery after ischemia-reperfusion injury. Am J Physiol Lung Cell Mol Physiol. 2019; 318(1):L78-L88. PMC: 6985877. DOI: 10.1152/ajplung.00221.2019. View

Caicedo A, Fritz V, Brondello J, Ayala M, Dennemont I, Abdellaoui N . MitoCeption as a new tool to assess the effects of mesenchymal stem/stromal cell mitochondria on cancer cell metabolism and function. Sci Rep. 2015; 5:9073. PMC: 4358056. DOI: 10.1038/srep09073. View

Cowan D, Yao R, Thedsanamoorthy J, Zurakowski D, Del Nido P, McCully J . Transit and integration of extracellular mitochondria in human heart cells. Sci Rep. 2017; 7(1):17450. PMC: 5727261. DOI: 10.1038/s41598-017-17813-0. View

Doenst T, Nguyen T, Abel E . Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res. 2013; 113(6):709-24. PMC: 3896379. DOI: 10.1161/CIRCRESAHA.113.300376. View

Wieckowski M, Giorgi C, Lebiedzinska M, Duszynski J, Pinton P . Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells. Nat Protoc. 2009; 4(11):1582-90. DOI: 10.1038/nprot.2009.151. View

Wu T, Sagullo E, Case D, Zheng X, Li Y, Hong J . Mitochondrial Transfer by Photothermal Nanoblade Restores Metabolite Profile in Mammalian Cells. Cell Metab. 2016; 23(5):921-9. PMC: 5062745. DOI: 10.1016/j.cmet.2016.04.007. View

Fillmore N, Lopaschuk G . Targeting mitochondrial oxidative metabolism as an approach to treat heart failure. Biochim Biophys Acta. 2012; 1833(4):857-65. DOI: 10.1016/j.bbamcr.2012.08.014. View

Rajapakse N, Shimizu K, Payne M, Busija D . Isolation and characterization of intact mitochondria from neonatal rat brain. Brain Res Brain Res Protoc. 2001; 8(3):176-83. DOI: 10.1016/s1385-299x(01)00108-8. View

McCully J, Levitsky S . Mitochondrial ATP-sensitive potassium channels in surgical cardioprotection. Arch Biochem Biophys. 2003; 420(2):237-45. DOI: 10.1016/j.abb.2003.06.003. View

10.

Black K, Barnett R, Bhasin M, Daly C, Dillon S, Libermann T . Microarray and proteomic analysis of the cardioprotective effects of cold blood cardioplegia in the mature and aged male and female. Physiol Genomics. 2012; 44(21):1027-41. PMC: 3524770. DOI: 10.1152/physiolgenomics.00011.2012. View

11.

McCully J, Bhasin M, Daly C, Guerrero M, Dillon S, Liberman T . Transcriptomic and proteomic analysis of global ischemia and cardioprotection in the rabbit heart. Physiol Genomics. 2009; 38(2):125-37. PMC: 2712218. DOI: 10.1152/physiolgenomics.00033.2009. View

12.

Claude A . Fractionation of mammalian liver cells by differential centrifugation; experimental procedures and results. J Exp Med. 2010; 84:61-89. View

13.

Fernandez-Vizarra E, Ferrin G, Perez-Martos A, Fernandez-Silva P, Zeviani M, Enriquez J . Isolation of mitochondria for biogenetical studies: An update. Mitochondrion. 2009; 10(3):253-62. DOI: 10.1016/j.mito.2009.12.148. View

14.

Galeano C, Qiu Z, Mishra A, Farnsworth S, Hemmi J, Moreira A . The Route by Which Intranasally Delivered Stem Cells Enter the Central Nervous System. Cell Transplant. 2018; 27(3):501-514. PMC: 6038044. DOI: 10.1177/0963689718754561. View

15.

Gollihue J, Patel S, Eldahan K, Cox D, Donahue R, Taylor B . Effects of Mitochondrial Transplantation on Bioenergetics, Cellular Incorporation, and Functional Recovery after Spinal Cord Injury. J Neurotrauma. 2018; 35(15):1800-1818. PMC: 6053898. DOI: 10.1089/neu.2017.5605. View

16.

Potter R, Groom A . Capillary diameter and geometry in cardiac and skeletal muscle studied by means of corrosion casts. Microvasc Res. 1983; 25(1):68-84. DOI: 10.1016/0026-2862(83)90044-4. View

17.

Rousou A, Ericsson M, Federman M, Levitsky S, McCully J . Opening of mitochondrial KATP channels enhances cardioprotection through the modulation of mitochondrial matrix volume, calcium accumulation, and respiration. Am J Physiol Heart Circ Physiol. 2004; 287(5):H1967-76. DOI: 10.1152/ajpheart.00338.2004. View

18.

Kim M, Hwang J, Yun C, Lee Y, Choi Y . Delivery of exogenous mitochondria via centrifugation enhances cellular metabolic function. Sci Rep. 2018; 8(1):3330. PMC: 5820364. DOI: 10.1038/s41598-018-21539-y. View

19.

Riva A, Tandler B, Loffredo F, Vazquez E, Hoppel C . Structural differences in two biochemically defined populations of cardiac mitochondria. Am J Physiol Heart Circ Physiol. 2005; 289(2):H868-72. DOI: 10.1152/ajpheart.00866.2004. View

20.

Clayton D, Shadel G . Purification of mitochondria by sucrose step density gradient centrifugation. Cold Spring Harb Protoc. 2014; 2014(10):pdb.prot080028. DOI: 10.1101/pdb.prot080028. View