Nav: Home

UCI team demonstrates ability to supercharge cells with mitochondrial transplantation

March 23, 2020

Irvine, Calif., March 23, 2020 - Researchers at the University of California, Irvine have shown that they can give cells a short-term boost of energy through mitochondrial transplantation. The team's study, published today in the Journal of the American Heart Association, suggests that mitochondrial transplantation could one day be employed to cure various cardiovascular, metabolic and neurodegenerative disorders - and even offer a new approach to the treatment of cancer.

"Mitochondria are the engines that drive many activities performed by our cells," said first author Paria Ali Pour, a UCI Ph.D. candidate in biomedical engineering. "If these organelles are mutated or deemed dysfunctional, the clinical manifestations are devastating, so we decided to study the intracellular consequences of mitochondrial transplantation and determine whether it would be a viable method for mitigating these adverse situations and helping patients."

There have been prior attempts to use mitochondrial transplantation in the form of direct injection to the heart muscle in infants with end-stage heart disease, but the UCI study is the first to seek data on the precise outcomes of mitochondrial transplantation at the cellular and subcellular levels. The JAHA article outlines the researchers' successful endeavor to achieve mitochondrial transplantation and how they systematically quantified its ability to boost cellular energy.

For the experiments, Ali Pour first isolated mitochondria by differential centrifugation, followed by transplantation through coincubation. Once the mitochondria had settled in their new host cells, she performed metabolic flux analysis to measure two key parameters: the oxygen consumption rate and the extracellular acidification rate, which provide important information about cellular metabolism and how well the cells are consuming/producing energy. The analyses were conducted at two, seven, 14 and 28 days.

"This is essentially a technique for studying how much oxygen is being consumed and protons emitted, or the total acidification rate, as the mitochondria produce adenosine triphosphate, the fuel for our cells," Ali Pour said. "Metabolic flux analysis is a comprehensive way to evaluate bioenergetics indices - the mechanisms by which cells process nutrients into energy and how well they do this. It helps us understand and make decisions about how mitochondrial transplantation affects cellular bioenergetics and metabolism."

She said the endosymbiosis origin of mitochondria is what inspired their work.

"Billions of years ago, mitochondria were prokaryotic bacteria that came into close contact with our ancestral eukaryotes. At that time, they were completely autonomous - to this day, mitochondrial DNA is separate and different from the genetic code in our cells' nuclei - but now they're semiautonomous," Ali Pour said. "That led us to hypothesize that if cells freely adopted mitochondria ages ago, it should - theoretically - be possible to also achieve this in a directed manner."

Her doctoral adviser and the paper's lead author, Dr. Arash Kheradvar, a UCI professor of biomedical engineering and medicine, said this is exactly what she succeeded in doing. "Paria was able to show in a definitive way, for the first time, that it is possible to control cell bioenergetics by changing the content of the mitochondria in a cardiomyocyte," Kheradvar said.

A key part of the team's experiments was to transplant healthy mitochondria from skeletal muscle cells into cardiomyocytes of a different breed (nonautologous) to focus on questions specifically related to cell bioenergetics. The studies confirmed that cellular bioenergetics improves in the host cells two days after transplantation, but this supercharged state diminishes later on.

"Regarding the viability of mitochondrial transplantation in different cell lines, we've done a lot of variations, including work with skeletal muscle cells, T-cells and cardiomyocytes," Ali Pour said. "We even tested the feasibility of transplanting mitochondria from rat cells to commercially available human cells, in our lab, to see if there's a mechanism that prevents such a procedure; we found that transplanting mitochondria between different species is also possible."

Next, the team plans to investigate whether the internalized mitochondria establish signaling with the cell's nucleus and whether they'll be adopted by the host on a long-term basis.

"We took a very cautious and fundamental approach with this project, because these cellular procedures, as a potential biotherapy, can have unknown and possibly grave consequences," Kheradvar said. "We didn't want to rush into human experimentation without knowing all of the potential ramifications in terms of safety and efficacy. Although we have a few hypotheses, nobody firmly knows what's happening when these mitochondria are introduced inside the cell - or whether there will be side effects. There are a lot of unanswered questions that need to be addressed."
-end-
Study co-author M. Cristina Kenney, a UCI professor of ophthalmology, also contributed significantly to the project, particularly on analyses and interpretation of metabolic flux data. Funding was provided by UCI's Council on Research, Computing and Libraries. Ali Pour was supported by a training grant from the National Institutes of Health for cardiovascular applied research and entrepreneurship.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs. It's located in one of the world's safest and most economically vibrant communities and is Orange County's second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.

Media access: Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UCI faculty and experts, subject to availability and university approval. For more UCI news, visit news.uci.edu. Additional resources for journalists may be found at
University of California - Irvine

Related Mitochondria Articles:

Inside mitochondria and their fascinating genome
EPFL scientists have observed -- for the first time in living cells -- the way mitochondria distribute their transcriptome throughout the cell, and it involves RNA granules that turn out to be highly fluid.
'Cheater mitochondria' may profit from cellular stress coping mechanisms
Cheating mitochondria may take advantage of cellular mechanisms for coping with food scarcity in a simple worm to persist, even though this can reduce the worm's wellbeing.
A ribosome odyssey in mitochondria
The ciliate mitoribosome structure provides new insights into the diversity of translation and its evolution.
Fireflies shed light on the function of mitochondria
By making mice bioluminescent, EPFL scientists have found a way to monitor the activity of mitochondria in living organisms.
First successful delivery of mitochondria to liver cells in animals
This experiment marks the first time researchers have ever successfully introduced mitochondria into specific cells in living animals.
Lack of mitochondria causes severe disease in children
Researchers at Karolinska Institutet in Sweden have discovered that excessive degradation of the power plants of our cells plays an important role in the onset of mitochondrial disease in children.
Unexpected insights into the dynamic structure of mitochondria
As power plants and energy stores, mitochondria are essential components of almost all cells in plants, fungi and animals.
Mitochondria are the 'canary in the coal mine' for cellular stress
Mitochondria, tiny structures present in most cells, are known for their energy-generating machinery.
Master regulator in mitochondria is critical for muscle function and repair
New study identifies how loss of mitochondrial protein MICU1 disrupts calcium balance and causes muscle atrophy and weakness.
Oxygen deficiency rewires mitochondria
Researchers slow the growth of pancreatic tumor cells.
More Mitochondria News and Mitochondria Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.