Tag Archives: Mitochondria

The Role of Brain Mitochondria in Initiating Sleep

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Mitochondria may have more functions than just energy production

CNRI/Science Photo Library

The energy-producing organelles in cells, known as mitochondria, may also influence sleep patterns. Research on fruit flies indicates that these organelles in the brain can promote sleep after prolonged wakefulness.

Scientists have begun to unravel the brain’s response to sleep deprivation. Findings include alterations in neuronal firing, changes in cell structure, and gene expression patterns. They have also pinpointed specific neurons triggered during sleep onset, yet the complexities of how these neurons act remain unclear.

“Sleep presents one of biology’s significant mysteries,” notes Gero Miesenböck of Oxford University. To delve deeper, he and his research team employed gene sequencing and fluorescent markers to observe gene activity in sleep-related neurons from around 1,000 female fruit flies (Drosophila melanogaster), which typically sleep for 13-16 hours, mainly during daylight hours.

The group allowed half the flies to rest overnight while keeping the others awake by gently agitating their containers or through genetic modifications that activated wake-promoting neurons with temperature increases.

Among the sleep-deprived flies, the researchers noted a surge in activity from sleep-inducing neurons that regulate genes tied to mitochondrial function and upkeep. The mitochondria displayed signs of stress as well, like fragmentation, damage repair efforts, and increased connections to nearby cellular structures.

This stress is likely due to the mitochondria continuing to generate energy even when neurons are inactive. The research indicates this can cause electron accumulation, leading to the formation of free radicals (unstable molecules capable of damaging DNA), thereby contributing to sleep pressure, according to Miesenböck. Once the flies were permitted to sleep, they repaired the mitochondrial damage.

Further findings showed that fragmented mitochondria in sleep-inducing neurons resulted in flies feeling less sleepy than usual and unable to recover after prolonged wakefulness. Conversely, flies engineered to facilitate mitochondrial fusion demonstrated superior repair capabilities, sleeping more than normal and bouncing back more effectively from sleep deprivation. This reinforces the hypothesis that mitochondria play a role in sleep regulation.

In another phase of the study, flies were genetically altered to enhance mitochondrial activity in response to light. This led to a 20-25% increase in sleep duration after just one hour of artificial light compared to the control group.

While this research focused on fruit fly neurons rather than human cells, mitochondria among different species share notable similarities. According to Ryan Mailloux at McGill University in Quebec, Canada, this adds credence to the idea that the energy production processes in mitochondria across various animals can underscore sleep pressure in humans.

This newfound insight could pave the way for novel treatments for sleep disorders. “This presents exciting possibilities for targeting these pathways to develop effective therapies for individuals struggling with sleep issues,” states Mailloux.

Michele Bereshi of Camerino University in Italy remarked, “This paper is certainly impactful and thought-provoking,” though he expresses concerns regarding the experimental design. “Sleep deprivation does not merely prolong wakefulness; it may introduce additional stressors that elicit cellular responses unrelated to the accumulation of sleep pressure.”

In response, Miesenböck explained that his team utilized diverse methods to keep the flies awake, including non-stressing temperature adjustments through gene editing, all achieving similar effects on mitochondrial activity. “What this study illustrates is that sleep homeostasis actively employs its own mitochondria to assess the need for sleep,” he asserts.

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Source: www.newscientist.com

Children Born from Donor Mitochondria Are Thriving Today

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Mitochondria supply energy to cells, yet mutations can lead to defects

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Eight young children are believed to be shielded from severe genetic disorders after being born through a procedure that replaces the mother’s faulty mitochondria with those from female donors.

Approximately 1 in 5,000 individuals inherit defective mitochondria, which are responsible for energy production in cells and passed down solely from mothers. Such defects can stem from genetic mutations leading to serious health issues like blindness, seizures, and even death. “Families face immense challenges with these conditions, as they are devastating,” said Bobby McFarland of Newcastle University in the UK.

In 2015, the UK became the first nation to sanction a technique known as pronuclear transfer for women at high risk of transmitting mitochondrial diseases who may not benefit from genetic testing prior to the transplant.

This technique involves utilizing eggs from both the mothers and donors, then fertilizing them with sperm from the father via IVF. After approximately 10 hours, the nuclei from both eggs are removed. This separates the crucial genetic material from the mitochondrial DNA.

The nucleus from the mother is subsequently inserted into the donor’s egg, resulting in an embryo that retains most of the genetic information from its biological parent while gaining mitochondria from the donor. It’s important to note that some maternal mitochondrial DNA could still be passed on unintentionally, as mentioned by Burt Smeet of Maastricht University in the Netherlands.

McFarland, who pioneered this approach with colleagues, has since employed the technique on 19 women possessing harmful mutations in over 80% of their mitochondria, typically the threshold for complications.

Following the transfer of the last embryo, seven women achieved pregnancies, resulting in the birth of eight healthy babies, including one set of twins.

Blood samples taken from the newborns were analyzed, revealing no harmful mitochondrial DNA mutations in five of them, while the other three showed only minimal levels. “The results have met our expectations,” noted Mike Murphy at Cambridge University.

Months or even years after undergoing nuclear transfer, some of the children have encountered challenges in reaching developmental milestones. Some have faced complications, potentially related to the transfer process. For instance, one child experienced elevated blood lipid levels and an irregular heartbeat, both of which were treated successfully, while another developed epilepsy at seven months, which resolved itself over time.

The research team intends to monitor the children to assess the long-term effects of this procedure.

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Source: www.newscientist.com

Cancer Cells Hijack Mitochondria from Neurons to Fuel Their Growth

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Neurons Growing Among Cancer Cell Cultures (Stained Green)

Simon Grelet and Gustavo Ayala

Cancer cells are known to hijack energy-generating components from neurons, facilitating their spread to remote locations. This groundbreaking discovery may enhance treatments for the most aggressive tumors.

“This marks the first instance of mitochondrial transfer from nerves to cancer cells,” states Elizabeth Lepasky, who is not directly linked to the study conducted at the Roswell Park Comprehensive Cancer Center in Buffalo, New York. “This signifies a pivotal advancement in cancer neuroscience, a rapidly evolving field.”

Prior knowledge indicated that both intratumor and adjacent tumors produce proteins and electrical impulses that promote cancer growth and dissemination. “A higher density of nerves within tumors correlates with a poorer prognosis,” says Simone Grelet from the University of Southern Alabama.

Earlier investigations have demonstrated that brain tumor cells can absorb mitochondria (the energy-producing organelles) from non-neuronal brain cells. However, the potential for tumor cells to extract mitochondria from neurons remained unclear, according to Grelet.

To explore this, Grelet and his team genetically modified breast cancer cells derived from mice to contain red fluorescent molecules and combined them with mouse neurons that had mitochondria labeled with green pigments in laboratory conditions. Imaging revealed that cancer cells can seize mitochondria from neurons within a matter of hours.

“Cancer cells extend their membranes to absorb mitochondria from neurons,” explains Grelet. “It’s akin to a lineup of mitochondria filtering through a narrow passage, entering the cancer cells sequentially.”

To assess whether this phenomenon occurs in vivo, the researchers injected red breast cancer cells into the mammary glands of female mice to induce tumor growth. They also genetically engineered the surrounding nerves to carry green mitochondria. Approximately one month later, 2% of the cancer cells in these tumors had taken up mitochondria from neurons.

Conversely, 14% of tumor cells that metastasized to the brain exhibited neuronal-derived mitochondria. This suggests that cancer cells acquiring mitochondria from nerves have a significant advantage over other cancer types. Further tests indicate that these mitochondria contribute to greater resilience against the physical and chemical challenges encountered in the bloodstream.

“Cancer cells face numerous hurdles in their migration,” remarks Repasky. “They must escape the primary tumor, navigate barriers to blood vessels, exit the bloodstream, and secure sufficient oxygen and nutrients at secondary sites. By appropriating mitochondria, it appears cancer cells can endure this tumultuous journey,” she adds.

To determine if this process also occurs in humans, researchers examined tumor samples from eight women with metastatic breast cancer. They discovered that tumor cells from distant sites contained, on average, 17% more mitochondria compared to those from breast tumors, suggesting that similar mechanisms are at play in patients, according to Grelet.

Moreover, the team analyzed human prostate tumor samples and observed that cancer cells near nerves contained significantly more mitochondria than those situated further away. “I believe this represents a common mechanism utilized by various tumor types,” asserts team member Gustavo Ayala from the University of Texas Health Science Center in Houston.

The findings indicate that inhibiting mitochondrial transfer could potentially curtail the spread of the deadliest tumors. “We are optimistic that this is achievable, at least for certain tumor types,” Repasky suggests. Ayala mentions that they are working towards developing a drug to facilitate this approach.

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Source: www.newscientist.com

Slowing Aging and Preventing Dementia Through Restoration of Brain Mitochondria

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Protein plaques in the brain may be caused by mitochondrial dysfunction

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If you own a car, you’ve probably noticed that your engine becomes less efficient over time. The farther you drive, the more fuel it takes to cover the same distance. Eventually, you’ll end up with so little power that you need a physical push to climb a gentle hill.

It is now becoming clear that much the same holds true for the human brain. Microscopic structures called mitochondria, found in all brain cells, are literally the engines of our thoughts and emotions. As we age, we find it increasingly difficult to generate enough energy to power mental activity. Worse, just like an old car leaves behind a cloud of smoke, the power source of our cells begins to produce unnecessary waste products that slowly pollute our brains. This means that mitochondrial dysfunction may underlie some of the most serious brain diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and motor neuron disease.

According to this “grand unified theory” of neurodegeneration, recharging neurons through restoration of their power plants can prolong healthy brain function. This idea has already inspired some exciting new treatments for age-related brain diseases, with multiple drug candidates under investigation. Some researchers are exploring the possibility of transplanting healthy mitochondria into damaged, aging brains to reactivate them. “If you keep replacing the parts in your car, it can last forever,” he says. claudio soto, a neurologist at the University of Texas Health Science Center at Houston. “So what happens if we try to run this…

Source: www.newscientist.com