An emerging area of research is the evolutionarily conserved transfer of mitochondria between cells. Yet researchers have lacked unique and universally accepted terms and practices to describe such transfers. Absent an agreed nomenclature and standard practices, different researchers may use different methods and terminology to describe the same event, or they may employ the same term that actually describe two different processes.

“Over the past few years, we have come to understand that mitochondria can be transferred from one cell to another, and that isolated mitochondria can be transplanted like an organ transplant,” said Keshav K. Singh, Ph.D., professor in the University of Alabama at Birmingham Department of Genetics. “Though the origins of mitochondria transfer are unclear, it has been observed in evolutionarily diverse eukaryotes, including yeast, mollusks, fish and rodents, as well as human cells. We are just beginning to understand how alterations in this process contribute to disease pathogenesis and how to harness mitochondria transfer and transplantation biology to develop new therapies.”

In 2024, Singh and Jonathan Brestoff, M.D., Ph.D., Washington University School of Medicine, Saint Louis, Missouri, set up an international consortium on mitochondria transfer and transplantation and led an international team of 31 researchers to develop consensus and recommendations about how to advance the field by providing common terminology and characterizations for the transfer or transplantation of mitochondria. Their consensus paper, “Recommendations for mitochondria transfer and transplantation nomenclature and characterization,” is published in the journal Nature Metabolism.

The paper begins with a brief history of the field — some foundational early discoveries, recent studies of mitochondrial transfer and development of therapeutic approaches, including cell engineering and clinical trials for children requiring extracorporeal membrane oxygenation.

The paper defines types of mitochondria transfer and mitochondria transplantation, and when both the donor and acceptor cell types are established in vivo, that defines a mitochondria transfer axis. The paper reviews methods to define mitochondria transfer, including mitochondria reporter proteins and dyes, methods to enforce transfer, and discussion of the fate of mitochondria after cell entry. Mechanism-based nomenclature is roughly grouped into contact-dependent mitochondria transfer, where the donor cell and recipient cell touch each other, and contact-independent mitochondria transfer.

The recommendations also review therapeutic approaches of mitochondria transplantation, including the definition of transplants; the types, durability, degree of engraftment and heterogeneity of transplants; cell engineering using extracellular mitochondria; and drugs that affect mitochondria transfer. Extracellular mitochondria are common in humans — for example there are about 3 billion to 12 billion extracellular mitochondria in a unit of blood platelets, a blood product that is routinely and safely transfused to patients intravenously.

The paper concludes that “the goal of this proposed nomenclature is to reduce the confusion that can be caused by the introduction of different names for similar processes or extracellular mitochondria subsets as this field has evolved. We recognize that mitochondria transfer and transplantation are very active areas of research and that it is possible that new findings and insights may necessitate updates to the proposed nomenclature.”

Singh has a long-standing interest in mitochondria. He was founding editor-in-chief of the journal Mitochondrion and the founder of the Society for Mitochondria Research and Medicine. In 2007 and 2009, his laboratory showed that isolated mouse mitochondria can be transferred to human cells by co-incubation, providing a proof of principle for transfer of mitochondria by diffusion, and that xeno-transplanted platelet mitochondria from an African American woman who suffered aggressive breast cancer at young age was able to recapitulate aggressiveness of breast cancer in mice. At that time, these findings were not appreciated by the field, Singh says.

The increase in physical activity was mainly seen in those doing semi-routine occupations such as bus driving or hairdressing, and routine occupations such as cleaning or waiting, or technical jobs. There was little change seen among people entering managerial or professional occupations.

The largest drop in levels of physical activity was seen among people who work from home — though their sleep levels did not change when they started work.

Young adulthood — ages 16 to 30 years — is an important time in terms of health. Although we are typically at our peak physical health, it is also a time when many risk factors for long term diseases such as heart disease, type 2 diabetes and cancer begin to develop.

Health guidelines recommend young adults get between seven and nine hours of sleep a night, engage in 150 minutes or more of moderate physical activity per week, and consume at least five portions of fruit and vegetables per day.

Young adulthood is also the time when most people start work, which changes their daily routines and activities, resources such as time and money, and social and physical environments — all of which affect health behaviours and health in later life.

To quantify the impact that starting work has on health-related behaviours, a team led by researchers at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge examined repeated data taken over time from more than 3,000 participants in the UK Household Longitudinal Study. All the participants were aged 16-30 years and started work for the first time between 2015 and 2023.

The results are published today in the International Journal of Behavioral Nutrition and Physical Activity.

Dr Eleanor Winpenny, who was based at the University of Cambridge when she carried out the work, but is now at Imperial College London, said: “We know about physical activity and sleep patterns among young people while they’re at school, but very little about what happens when they start work. Given the impact that work can have on our lives — and the lasting impacts this can have on our health — it’s important to try and understand what happens at this transition.”

The analysis showed that when people started work, their physical activity increased by an amount equivalent to around 28 min of moderate activity (such as cycling) per day on average — but then decreased each year after starting work by around 7 min per day.

The biggest increase was among males — up by an equivalent of around 45 min of moderate activity per day compared to an increase of around 16 min for females. People who did not have a university degree also showed a greater increase in physical activity compared to those with a university degree — equivalent to around a 42 min increase of moderate physical activity per day compared to 15 min per day.

Working from home, however, appeared to be associated with an initial decrease in physical activity, equivalent to around 32 min of moderate activity per day.

When young adults started work, the amount of time they slept per night dropped immediately by almost 10 minutes and remained stable at this level over time; however, people without a degree showed a continuing decrease of about 3 minutes of sleep per night each year after starting work, while those with a degree slowly increased back to their pre-work sleep levels.

There was little change in the amount of fruit and vegetables consumed after starting work.

Alena Oxenham, from the MRC Epidemiology Unit, said: “Beginning work can have a profound impact on our lifestyles and on behaviours that might make a difference to our health, if not immediately then later in life.

“Although we found that people tend to do more physical activity when they begin work, which is good news, these are averages, and some people — particularly those who work from home and, to a lesser degree, those with office-based jobs — may do less.

“If we want to stay healthy throughout our lives, we need to remember that keeping active is an important way of helping us achieve this goal. Those working at home might want to consider incorporating physical activity into their day, for example by going for a walk before or after work, or during a lunch break.”

Dr Winpenny added: “Workplaces provide an opportunity to create environments and cultures that support healthier diets, more physical activity and better sleep for young adults. This could result in healthier employees and fewer sick days in the immediate term, but also have long term benefits, helping prevent health issues in later life.”

The findings, presented today at the American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Annual Symposium and published in Nature Medicine, demonstrated a 60.9% overall response rate (ORR) with the three-drug combination compared to 40% with the standard-of-care (SOC) treatment — chemotherapy with or without bevacizumab. In the experimental arm, 68.7% of patients had a duration of response of at least six months, compared to 34.1% of patients in the SOC arm.

Data from this multi-institutional collaboration across 28 countries supported the accelerated approval of this combination by the Food and Drug Administration (FDA) in Dec. 2024, providing an effective new first-line treatment option for patients with BRAF V600E-mutant mCRC.

“Chemotherapy has had limited efficacy as a first-line treatment in controlling the aggressive tumor growth we see in patients with this mutation,” said co-principal investigator Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology and associate vice president of Translational Integration at MD Anderson. “This new regimen highlights the importance of combining dual-targeted therapy with chemotherapy to improve patient outcomes in the first-line setting, and the durable responses are a significant development as we work to improve quality of life for these patients.”

More than 150,000 people are diagnosed with colorectal cancer each year, making it the fourth most common cancer in the U.S., according to the National Cancer Institute. BRAF mutations occur in approximately 8-12% of cases and are associated with aggressive tumor growth, low efficacy from SOC treatments and a poor prognosis, with a median overall survival less than 12 months. Previously, there were no first-line targeted therapies approved for patients with BRAF V600E-mutant mCRC.

The BREAKWATER trial was one of the first studies to utilize the FDA’s Project FrontRunner, an initiative to encourage the evaluation of therapies in earlier clinical settings for advanced cancers rather than after patients received numerous previous treatments.

The trial enrolled patients who were at least 16 years of age with previously untreated BRAF V600E-mutant mCRC. Patients were randomized equally to one of three treatment arms: SOC chemotherapy with or without bevacizumab; a dual combination of encorafenib plus cetuximab; or a triple combination of encorafenib, cetuximab and mFOLFOX6.

When researchers analyzed patient subgroups on the trial, the triple combination showed benefits across important groups, including patients with cancer spread to three or more organs and those with liver metastases.

“These results support this combination as a new first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” Kopetz said. “It also highlights the importance of swiftly identifying molecular subtypes of colorectal cancer at diagnosis to optimize treatment strategies for our patients.”

The safety profile of this combination was consistent with the known safety profile of each respective drug. No new safety signals were identified. The most common adverse reactions included nausea, rash, fatigue, vomiting, abdominal pain, diarrhea and decreased appetite, all of which were reported in at least 25% of patients and were similar between arms.

Final calculations of progression-free survival and overall survival will be formally assessed in the next phase of the trial. Future analyses of this trial may shed light on predictive biomarkers for this combination therapy.

The study was sponsored by Pfizer Inc., and Kopetz disclosed consulting for Pfizer and receiving research funding from the company.

Researchers from Arizona State University, along with their colleagues from the National University of the Peruvian Amazon, have identified an unknown family of microbes uniquely adapted to the waterlogged, low-oxygen conditions of tropical peatlands in Peru’s northwestern Amazonian rainforest.

The new research shows these microbes have a dual role in the carbon cycle and the potential to either moderate or intensify climate change. This process can either stabilize carbon for long-term storage or release it into the atmosphere as greenhouse gases, particularly CO2 and methane.

Under stable conditions, these microbes enable peatlands to act as vast carbon reservoirs, sequestering carbon and reducing climate risks. However, environmental shifts, including drought and warming, can trigger their activity, accelerating global climate change.

And, continued human-caused disruption of the natural peatland ecosystem could release 500 million tons of carbon by the end of the century — roughly equivalent to 5% of the world’s annual fossil fuel emissions.

“The microbial universe of the Amazon peatlands is vast in space and time, has been hidden by their remote locations, and has been severely under-studied in their local and global contributions, but thanks to local partnerships, we can now visit and study these key ecosystems,” says Hinsby Cadillo Quiroz, corresponding author of the new study and a researcher with the Biodesign Swette Center for Environmental Biotechnology at ASU.

“Our work is finding incredible organisms adapted to this environment, and several of them provide unique and important services — from carbon stabilization or recycling to carbon monoxide detoxification and others.”

Cadillo-Quiroz is also a researcher with the Biodesign Center for Fundamental and Applied Microbiomics and the ASU School of Life Sciences. ASU colleague Michael J. Pavia is the lead author of the investigation.

The study, appearing in the American Society for Microbiology journal Microbiology Spectrum, emphasizes the importance of protecting tropical peatlands to stabilize one of the planet’s most significant carbon storage systems and underscores the subtle interplay between microbial life and global climate regulation.

Why peatlands are crucial for climate stability

The Amazonian peatlands are among the planet’s largest carbon vaults, storing an estimated 3.1 billion tons of carbon in their dense, saturated soils — roughly twice the carbon stored in all the world’s forests. Peatlands are critical for global carbon storage because their waterlogged conditions slow decomposition, allowing organic material to accumulate over thousands of years. These ecosystems play a crucial role in regulating greenhouse gas emissions and influencing global climate patterns.

Building on earlier research, the current study describes newly identified microbes — part of the ancient Bathyarchaeia group that forms a complex network essential to the functioning of this ecosystem. The study highlights the remarkable abilities of these microorganisms to regulate carbon cycling in peatlands. Unlike most organisms, these microbes can thrive in extreme conditions, including environments with little to no oxygen, thanks to their metabolic flexibility.

The microbes are found in the Pastaza-Marañón Foreland Basin — a vital peatland in the northwestern Amazon rainforest of Peru. Encompassing approximately 100,000 square kilometers, the basin includes vast tracts of flooded rainforest and swamps underlain by ancient peat.

These peatland microbes consume carbon monoxide — metabolizing a gas toxic to many organisms — and convert it into energy, simultaneously reducing carbon toxicity in the environment. By breaking down carbon compounds, they produce hydrogen and CO2 that other microbes use to generate methane. Their ability to survive both oxygen-rich and oxygen-poor conditions makes them well suited to Amazonian environments, where water levels and oxygen availability fluctuate throughout the year.

However, shifts in rainfall, temperature and human activities, including deforestation and mining, are disrupting this delicate balance, causing peatlands to release greenhouse gases like carbon dioxide and methane.

Climate connection

While tropical peatlands currently act as carbon sinks, absorbing more carbon than they release, they are increasingly vulnerable to climate change. Rising temperatures and altered rainfall patterns could dry out these peatlands, turning them into carbon sources.

The release of billions of tons of carbon dioxide and methane from peatlands would significantly amplify global warming. The findings emphasize the urgent need to protect tropical peatlands from human activities and climate-induced stress.

The researchers advocate for sustainable land management, including reducing deforestation, drainage and mining activities in peatlands to prevent disruptions. Further investigation of microbial communities is needed to better understand their roles in carbon and nutrient cycling.

Tracking changes in temperature, rainfall and ecosystem dynamics is also necessary to predict future impacts on peatlands.

New directions

The discovery of highly adaptable peatland microbes advances our understanding of microbial diversity and underscores the resilience of life in extreme environments. These microbes represent a key piece of the puzzle in addressing global climate challenges, showing how the tiniest organisms can have an outsized impact on Earth’s systems.

This research, supported by the National Science Foundation, marks a significant step forward in understanding the critical role of tropical peatlands and their microbial inhabitants in global carbon cycling. As climate change continues to reshape our planet, these hidden ecosystems hold lessons that may help safeguard our future.

Drug delivery systems often face two critical challenges: poor solubility and inefficient delivery within the body. Many drugs do not dissolve well, making it difficult for them to reach their intended targets. Furthermore, current delivery systems waste a significant portion of the drug during preparation — only 5-10% of the drug is successfully loaded, leading to less effective treatments.

Peptide Helpers

The research team has developed a novel solution by designing peptides — short strings of amino acids — to bind with specific drugs and create therapeutic nanoparticles. These nanoparticles are primarily composed of the drug, with a thin peptide coating that improves solubility, enhances stability in the body, and optimizes delivery to targeted areas. Remarkably, this approach achieves drug loadings of up to 98%, a dramatic improvement over traditional methods.

By using a combination of computer models and laboratory tests, new drug/peptide nanoparticles where identified. They subsequently demonstrated remarkable results in leukemia models. The nanoparticles were more effective at shrinking tumors compared to the drugs alone. Additionally, their high efficiency allows for lower doses of drugs, potentially reducing the side effects.

“Peptides, which are designed molecules made from the same building blocks as the proteins in our body, are extremely versatile,” said Co-Principal Investigator Rein Ulijn, director of the Nanoscience Initiative at CUNY ASRC and a chemistry professor at Hunter College. “We thought they could be useful in solving two big problems seen in many drugs: poor solubility and inefficient delivery. By designing a peptide that binds the drug while enhancing its solubility, we were able to create nanoparticles with very high loading.”

Customizable Technology

This innovation holds significant potential because peptides can be customized to enhance the effectiveness of various drugs. Given the vast range of possible interactions in peptide design, it may be feasible to tailor peptides for specific drugs, extending their applicability beyond cancer treatments.

“This breakthrough enables the development of better precision medicines,” said Co-Principal Investigator Daniel Heller,head of the Cancer Nanomedicine Laboratory at Memorial Sloan Kettering Cancer Center’s Molecular Pharmacology Program. “Using specially designed peptides, we can build nanomedicines that make existing drugs more effective and less toxic and even enable the development of drugs that might not be able to work without these nanoparticles.”

Naxhije “Gia” Berisha, a former CUNY Graduate Center Ph.D. student who performed much of the experimental work, highlighted the potential of the peptide approach: “We used experimental testing to identify promising peptides and computational modeling to analyze their interactions with therapeutic molecules,” she said “It’s incredible to see how simple variations in peptide sequence could match specific drugs. This suggests there may be a peptide match for every drug, potentially revolutionizing the way medicines are delivered.”

Looking Ahead

The research team is now adopting lab automation methods to further refine and accelerate the peptide-drug matching process. Their next steps include verifying the approach’s potential in a wider range of diseases. If successful, this innovation could lead to more effective treatments, reduced side effects, and significant cost savings in drug development.