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16th World Congress on Targeting Mitochondria | 2025

Imaging Method Evaluates Cell Functional Changes and Wound Healing

Optical redox ratio maps of fibroblasts isolated from young and aged rats. Red regions correspond to high redox ratios, while blue regions correspond to low ratios. Images courtesy of Olivia Kolenc and Kyle Quinn.

Kyle Quinn, assistant professor of biomedical engineering at the University of Arkansas, has published a review highlighting recent advances in autofluorescence imaging and discussing its role in evaluating cell metabolism.

Autofluorescence is the emission of light by molecules naturally present in cells and tissue when those molecules have absorbed light.

Quinn and graduate student Olivia Kolenc have published an article in Antioxidants & Redox Signaling, explaining that human cells and tissues contain naturally fluorescent molecules that can be imaged and used to assess cell metabolism for a broad spectrum of biomedical applications, including tissue engineering and regenerative medicine.

Autofluorescence imaging of these naturally fluorescent molecules – nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) – can allow researchers to assess the structural organization of mitochondria and biochemical details related to cell metabolism. This can be done through a measurement called an optical redox ratio, which quantifies the relative concentrations of NADH and FAD. The three-dimensional distribution of NADH and FAD within cells can be quantified non-invasively in living tissue by using a multiphoton microscope.

Mitochondria are the organelles – or specialized structures – within cells that are responsible for respiration and energy production.

Traditionally, this imaging technique has been used to monitor cell metabolism during hypoxia and cancer development, Quinn said. But he and Kolenc expect that continued improvement in instrumentation and analysis with these methods will lead to wider applications and further advances in basic science, preclinical research and clinical management of disease. For example, part of Quinn’s research focuses on applying this imaging technique to the study of wound healing.

Quinn is also a co-author of a new study by researchers at Tufts University, where he was a postdoctoral fellow after receiving his doctorate at the University of Pennsylvania. The study highlights some of these new applications and methods for autofluorescence imaging of NADH and FAD.

“Autofluorescence intensity can be a useful metric to noninvasively assess metabolic and functional cellular changes for a variety of biochemical applications,” Quinn said. “We here at the U of A are particularly excited about its use in evaluating wound healing.”

Quinn’s research is supported by the National Institutes of Health, Department of Defense, and the Arkansas Biosciences Insititute. In September of 2017, he received a $1.7 million grant from the NIH to continue developing autofluorescence imaging methods to quantify and understand age-related delays in skin wound healing.

Also in 2017, Quinn published research demonstrating that during the weeks following a heart attack, the injured heart wall acquires more collagen fibers that are significantly less stiff due to a lack of naturally fluorescent fiber crosslinks. That study appeared in Nature Publishing Group’s Scientific Reports.

News source: https://researchfrontiers.uark.edu

Mitochondria behind blood cell formation

New Northwestern Medicine research published in Nature Cell Biology has shown that mitochondria, traditionally known for their role creating energy in cells, also play an important role in hematopoiesis, the body's process for creating new blood cells."Historically, mitochondria are viewed as ATP—energy—producing organelles," explained principal investigator Navdeep Chandel, PhD, the David W. Cugell Professor of Medicine in the Division of Pulmonary and Critical Care Medicine. "Previously, my laboratory provided evidence that mitochondria can dictate cell function or fate independent of ATP production. We established the idea that mitochondria are signaling organelles."In the current study, Chandel's team, including post-doctoral fellow Elena Ansó, PhD, and graduate students Sam Weinberg and Lauren Diebold, demonstrated that mitochondria control hematopoietic stem cell fate by preventing the generation of a metabolite called 2-hydroxyglutarate (2HG). The scientists showed that mice with stem cells deficient in mitochondrial function cannot generate blood cells due to elevated levels of 2HG, which causes histone and DNA hyper-methylation."This is a great example of two laboratories complementing their expertise to work on a project," said Chandel, also a professor of Cell and Molecular Biology and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.Paul Schumacker, PhD, professor of Pediatrics, Cell and Molecular Biology and Medicine, was also a co-author on the paper.Chandel co-authored an accompanying paper in Nature Cell Biology, led by Jian Xu, PhD, at the University of Texas Southwestern Medical Center, which demonstrated that initiation of erythropoiesis, the production of red blood cells specifically, requires functional mitochondria."These two studies collectively support the idea that metabolism dictates stem cell fate, which is a rapidly evolving subject matter," said Chandel, who recently wrote a review in Nature Cell Biology highlighting this idea. "An important implication of this work is that diseases linked to mitochondrial dysfunction like neurodegeneration or normal aging process might be due to elevation in metabolites like 2HG."

Read more at: https://phys.org/news/2017-06-mitochondria-blood-cell-formation.html#

Mitochondrial replacement moratorium should be reconsidered, researchers say

Mothers with mitochondrial DNA mutations often give birth to children who face incurable and fatal illnesses. But a much-studied form of mitochondrial replacement (MR) could prevent the transmission of such diseases from mothers to children, researchers say.

For that reason, two researchers argue that the U.S. moratorium that includes MR should be reconsidered through a process that engages the public, medical professionals, the U.S. Food and Drug Administration and Congress.

The authors -- Eli Adashi, a professor of medical science at Brown University's Warren Alpert Medical School, and Harvard Law School professor I. Glenn Cohen -- make their case in a March 2018 commentary in Obstetrics & Gynecology.

Such a process could clarify the benefits of the procedure -- namely, the births of healthy children -- and decouple it from misplaced concerns about genetic editing of embryos, the authors wrote. MR therapy simply replaces mutation-bearing mitochondria in oocytes (unfertilized, un-implanted eggs) with donated mutation-free mitochondria.

"A thousand children are born every year in the U.S. with serious, life-threatening issues that in a better world could be prevented by mitochondrial replacement," Adashi said. "While I have every respect for the sanctity of life, this issue is not about the sanctity of life. There is an inherent hypocrisy in holding this procedure hostage at the expense of 1,000 children each year who are doomed to die a painful death. There is nothing anti-life about the procedure, because no embryo is destroyed, and the life of baby is saved."

The moratorium

In 2016, legislation was passed that prohibits U.S.-based research in which a human embryo is intentionally created or modified, the study notes. While MR does not modify or "enhance" the nuclear genome, according to Adashi, replacing mutation-bearing mitochondria with donated mutation-free mitochondria falls under the general category of procedures prohibited by the moratorium.

In their commentary, Adashi and Cohen point out that the authors of the legislation are anonymous and that no congressional hearings, floor discussions or public engagement took place before its passage.

The authors surmise that the legislation may have been intended primarily to prevent embryo loss, a concern that does not apply to MR. A public process of reevaluating MR's inclusion in the moratorium could help to clarify that MR takes place before an embryo exists. The donated mitochondria are placed within unfertilized eggs, which can then be fertilized so that women can give birth to genetically related, disease-free children.

It is possible, Adashi said, that a misunderstanding of the sweeping nature of the legislation inadvertently bars the procedure.

"Mitochondrial replacement is best viewed as life-enhancing in its outlook by dint of its capacity to alleviate human suffering in a context where no other option exists," the authors wrote.

Impact of the moratorium

The moratorium deprives affected American families of the opportunity to prevent inherited, incurable and agonizing mitochondrial disease in their children, the authors contend.

Mitochondrial diseases include Leigh syndrome, a progressive and fatal disorder characterized by lesions on the brain that may lead to heart, kidney, vision and breathing complications, and Alpers Disease, a neurologic illness that causes seizures, dementia, spasticity, blindness, liver dysfunction and cerebral degeneration.

The moratorium may also induce American families to seek care outside of the country, according to Adashi and Cohen. They noted that a U.S.-led team in Mexico may have prevented Leigh syndrome in a child by replacing the mutation-bearing mitochondria of oocytes with donated mutation-free oocytes.

"This development calls into question the regulatory utility of a national moratorium in a globalized world wherein cross-border care is increasingly prevalent," Adashi and Cohen wrote in the study. It also creates risks, the authors assert, because there is no FDA oversight of these procedures that take place outside the U.S. border.

A path forward

Adashi and Cohen recommend that a coalition of patient and advocacy groups, medical professionals and legislators convene congressional hearings on the prevention of mitochondrial diseases. They also suggest convening a public meeting of the FDA's Cellular, Tissue and Gene Therapies Advisory Committee, charged with regulating reproductive technologies, to review the state-of-the-art procedure.

They also recommend stringent FDA oversight, the conditional approval of biologic licensing applications, clinic-specific licensing, possible sunset contingency provisions, and long-term intergenerational follow-up of the children of mothers who undergo mitochondrial replacement to determine the continuing safety and efficacy of the intervention.

In the U.K., a careful 15-year vetting process resulted in a vote in Parliament that approved MR under stringent regulatory oversight. In the U.S., on the other hand, "Congress legislated a statute that prohibits the FDA from adjudicating research into a range of procedures hereby treating the issue with a broad brush," Adashi said.

"They spent 15 years studying it -- the science, the safety, the ethics -- and they asked the British public what they thought," he added. "Now MR is legal but regulated by an agency that has been proceeding very cautiously, with just one clinic licensed to perform the procedure."

What this means, Adashi said, is that parents who are at risk for transmitting mitochondrial disease to their children may now undergo MR and have children who are not born with agonizing and untreatable diseases. American parents, Adashi and Cohen wrote in the commentary, deserve nothing less.

News source: https://www.sciencedaily.com

Can Vitamins and Supplements Help Patients with Mitochondrial Disease?

Defects in mitochondria, the tiny structures that power our cells by functioning as biological batteries, cause an array of complex, often life-threatening disorders that can affect any and all organs and systems. In the absence of validated, effective drug treatments, patients with mitochondrial disease often take a variety of vitamins and supplements, substances that are largely unstandardized, unregulated and unproven.

Experts in mitochondrial medicine propose to remedy that situation, calling for systematic scientific studies in cells and animals to lay the foundation for clinical trials of precise nutritional interventions for patients with energy deficiency diseases.

“We’re aiming to raise the bar for clinical treatments,” said Marni J. Falk, MD, Executive Director of the Mitochondrial Medicine Frontier Program at Children’s Hospital of Philadelphia (CHOP). Falk co-authored a new analysis of nutritional interventions for mitochondrial disorders published Nov. 3 in the Annual Review of Pathology: Mechanisms of Disease. “Our major objectives were to review the basic scientific evidence for compounds already being used in mitochondrial disease patients and to advocate a framework for rigorously evaluating their safety and efficacy in this population.”

The review article represents the collaborative effort of expert co-authors from eight centers, including first author Adam J. Kuszak, PhD, of the Office of Dietary Supplements of the National Institute of Health (NIH). The current effort grew out of a 2014 NIH meeting focused on developing an evidence base for nutritional interventions in primary mitochondrial disorders.

“Our analysis made it clear how much more we need to learn about developing effective nutritional treatments for mitochondrial disease,” said co-author Zarazuela Zolkipli-Cunningham, MBChBD, a neuromuscular specialist and attending physician in CHOP’s Mitochondrial Medicine Frontier Program. “There’s a large gap between the compounds that patients are routinely using and the degree to which those compounds have been scientifically tested.”

For instance, Zolkipli-Cunningham pointed to an “astounding variety” of the supplement coenzyme Q₁₀ (CoQ₁₀), sold over the counter in diverse versions and dosages. It is marketed as an antioxidant to reduce biological damage from reactive oxidant molecules.

However, she pointed out, there is no definitive evidence for health benefits from CoQ₁₀. Moreover, there are no standardized formulations for this supplement, so patients may receive widely varying ingredients from one product to another. A third consideration is that a given supplement may act differently in a healthy consumer than in an individual with a mitochondrial disorder, because defects in mitochondria have wide-ranging effects on cellular function. Finally, supplements may act very differently across different subtypes of mitochondrial disease.

“Anything that affects cellular function is biologically acting as a drug, whether you obtain it from a pharmacy or a health food store,” said Falk. “However, unlike prescription medications, which are closely regulated and standardized by the U.S. Food and Drug Administration, vitamins, dietary supplements, and medical foods are considered in our country to be in a separate regulatory category with much less stringent requirements. Their manufacturing standards are not as tightly regulated, and their claims are limited to optimizing general public health, not to treating specific diseases. So we know a lot less about their safety and efficacy in patients.”

To read the complete news, please follow the link to original news: http://www.chop.edu/news/can-vitamins-and-supplements-help-patients-mitochondrial-disease

'Natural insecticide' kills advanced prostate cancer cells: A Mitochondria issue

Researchers reveal how a 'natural insecticide' can destroy advanced prostate cancer cells.

One of the hallmarks of advanced prostate cancer is a faulty PTEN tumor suppressor gene. Now, after screening compounds for their effect on cells lacking PTEN, scientists have discovered that a natural insecticide called deguelin can kill such cells by disrupting their energy supply.

Deguelin belongs to a class of drugs known as mitochondrial inhibitors. The drugs block the action of mitochondria.

Mitochondria are the tiny compartments inside cells that convert glucose in the cell into molecules of adenosine triphosphate (ATP), which serve as units of energy for fueling the various workings of the cell.

Scientists at Cold Spring Harbor Laboratory in New York found that treating cells lacking PTEN with some types of mitochondrial inhibitor caused the cells to use glucose from their environment to make ATP and then transport it into their mitochondria to preserve them.

It is as though cells without PTEN, explains study leader Lloyd Trotman, a professor at Cold Spring Harbor Laboratory, are driven to "consume vast quantities of glucose" to help their mitochondria survive. They do this to the point where they run out of fuel and die.

The researchers describe their work — which included the use of a genetic mouse model of metastatic prostate cancer that was developed by Prof. Trotman's group — in a paper now published in the journal Cell Reports.

They suggest that their findings show that, at the right dose, certain mitochondrial inhibitors such as deguelin — and another that they identified called rotenone — may be able to kill prostate cancer cells without harming healthy cells.

However, they also note that the timing and conditions have to be just right – for example, the drug would not work if glucose levels are high.

"The hope is," Prof. Trotman explains, "that carefully timed administration of these drugs can generate a much better window of selective killing."

News source: https://www.medicalnewstoday.com

Photo Credit: medicalnewstodat