Mitochondrial Transfer by Photothermal Nanoblade Restores Metabolite Profile in Mammalian Cells

Ting-Hsiang Wu; Enrico Sagullo; Dana Case; Xin Zheng; Yanjing Li; Jason S Hong; Tara TeSlaa; Alexander N Patananan; J Michael McCaffery; Kayvan Niazi; Daniel Braas; Carla M Koehler; Thomas G Graeber; Pei-Yu Chiou; Michael A Teitell

doi:10.1016/j.cmet.2016.04.007

Mitochondrial Transfer by Photothermal Nanoblade Restores Metabolite Profile in Mammalian Cells

Cell Metab. 2016 May 10;23(5):921-9. doi: 10.1016/j.cmet.2016.04.007.

Authors

Affiliations

¹ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁴ Integrated Imaging Center, Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
⁵ NantWorks, LLC, Culver City, CA 90232, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁸ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA Metabolomics Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Crump Institute for Molecular Imaging, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁹ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: pychiou@seas.ucla.edu.
¹⁰ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: mteitell@ucla.edu.

Abstract

mtDNA sequence alterations are challenging to generate but desirable for basic studies and potential correction of mtDNA diseases. Here, we report a new method for transferring isolated mitochondria into somatic mammalian cells using a photothermal nanoblade, which bypasses endocytosis and cell fusion. The nanoblade rescued the pyrimidine auxotroph phenotype and respiration of ρ0 cells that lack mtDNA. Three stable isogenic nanoblade-rescued clones grown in uridine-free medium showed distinct bioenergetics profiles. Rescue lines 1 and 3 reestablished nucleus-encoded anapleurotic and catapleurotic enzyme gene expression patterns and had metabolite profiles similar to the parent cells from which the ρ0 recipient cells were derived. By contrast, rescue line 2 retained a ρ0 cell metabolic phenotype despite growth in uridine-free selection. The known influence of metabolite levels on cellular processes, including epigenome modifications and gene expression, suggests metabolite profiling can help assess the quality and function of mtDNA-modified cells.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Base Sequence
Cell Line, Tumor
Clone Cells
DNA, Mitochondrial / genetics
Energy Metabolism
Gene Expression Regulation
Humans
Light*
Mammals / metabolism*
Metabolome* / genetics
Metabolomics
Mitochondria / metabolism*
Nanoparticles / chemistry*
Reproducibility of Results
Temperature*

Substances

DNA, Mitochondrial

Abstract

Publication types

MeSH terms

Substances

Grants and funding