USA scientist challenges study on mitochondrial DNA inheritance

Mikhail Alexeyev Ph.D., center, and research technologists Natalya Kozhukhar, Ph.D., and Rafik Fayzulin, Ph.D., study mitochondrial DNA in the lab.

By Lindsay Hughes 

A scientist at the University of South Alabama has challenged a key conclusion of a 2023 study on the maternal inheritance of mitochondrial DNA. 

Mikhail Alexeyev, Ph.D., a professor of physiology and cell biology at the Frederick P. Whiddon College of Medicine, provides a critical analysis of the study in Nature Genetics, a high-impact scientific journal. His article, “An alternative model for maternal mtDNA inheritance,” is published in the journal’s March 2025 issue.

Understanding how mitochondrial DNA (mtDNA) is inherited “will inform our approaches to genetic counseling for mitochondrial disease and male infertility, as well as the development of gene therapy strategies for treating mitochondrial disorders,” Alexeyev said.

In most species, mtDNA is inherited from a single parent. The current understanding is that, in humans, mtDNA is inherited exclusively from the mother. Scientists have identified several mechanisms in different species that ensure uniparental inheritance of mtDNA. However, it is still unclear how these mechanisms work in humans. Interestingly, studies have shown that mtDNA content in human sperm inversely correlates with fertility: As the amount of mtDNA in sperm increases, fertility tends to decrease. 

The study that Alexeyev challenges was conducted by researchers at Thomas Jefferson University in Philadelphia and published in the September 2023 issue of Nature Genetics. The authors demonstrated that human sperm contains little to no mtDNA, less than previously thought. They also confirmed earlier findings that sperm were missing two proteins – POLG and POLRMT – that are essential for maintaining mtDNA. 

Another important finding in the Jefferson University study involved a protein called TFAM. Normally, TFAM is found in the mitochondria, the energy-producing parts of cells, where it plays a key role in maintaining and regulating mtDNA. However, in sperm, TFAM is primarily located in other areas of the cell, like the nucleus (the cell’s control center) and cytosol (the fluid in the cell that surrounds the organelles). 

The researchers also found that TFAM is chemically modified through phosphorylation, a process in which a phosphate group is added to the protein. They suggest that this modification prevents TFAM from entering the mitochondria, which may account for the loss of mtDNA in sperm. In other words, this alteration in TFAM’s location and function could explain why sperm don’t pass on mitochondrial DNA. 

In his critique of the Jefferson University study, Alexeyev invokes Occam’s razor, a principle that suggests the simplest explanation – the one that requires the fewest assumptions – is usually the best. He proposes a more straightforward model: “Sperm lacks mtDNA because it is missing POLG and POLRMT, as well as two other proteins, TFB2M and TWNK,” he explained. “In the absence of any of these four proteins, mtDNA is lost, and the combined loss of all four presents a compelling argument – one that our reviewers acknowledged.”

Alexeyev said the Jefferson University model is difficult to prove but can be easily falsified. “For example, the paper provides evidence that as many as three proteins (TFAM, POLG and POLRMT) and potentially as many as five (adding TFB2M and TWNK) essential for mtDNA maintenance might be missing from sperm mitochondria. If so,” he asks, “why would TFAM alone be responsible for mtDNA loss?”

In response to Alexeyev’s criticism, the authors put forward a hypothesis that TFAM, unlike the other four proteins, physically shields mtDNA from nucleases. Nucleases are enzymes that are designed to break apart the nucleotides that make up the nucleic acids DNA and RNA. Therefore, TFAM relocalization from mitochondria would have the additional consequence of making mtDNA vulnerable to attack by nucleases, which leads to accelerated mtDNA loss.

“In our rebuttal, we point out that this assumption is contradicted by experimental evidence,” Alexeyev said. “Indeed, mtDNA remains accessible to mitochondrially expressed nucleases. We and others have used this accessibility to develop methods for mtDNA elimination from cells.”

Recently, the Alexeyev lab used the GeneSwap method, as described in their paper “A method for in situ reverse genetic analysis of proteins involved in mtDNA replication,” to substitute normal TFAM in cells with mutant forms that mimic the phosphorylated version found in sperm. These modified cells retain mtDNA, contradicting the model proposed by the Jefferson University team.

Alexeyev's work, including his use of innovative gene-editing techniques, may help refine our understanding of mtDNA inheritance and its role in human health. If researchers can uncover the precise mechanisms behind mtDNA inheritance, it could open new avenues for gene therapy and treatment strategies.

Read the full article in Nature Genetics: “An alternative model for maternal mtDNA inheritance.”

EDGE session focuses on communication, collaboration and 'Crucial Conversations'

From left, Brittany Seals, Ed.D.; Brittany Brown, MSN, RN, NE-BC; Marcina Lang, MPA; Megan Durbin; and Keniesha Fields facilitated the session.

The second session in the EDGE for Success series delivered powerful takeaways on communication, feedback, and trust-building – essentials for thriving in any workplace, regardless of title or role. 

The session was facilitated by a dynamic team: Marcina Lang, MPA, senior manager of COM support services; Brittany Brown, MSN, RN, NE-BC, director of operations for internal medicine; Megan Durbin, clinical trials budget coordinator; Brittany Seals, Ed.D., assistant director of admissions; and Keniesha Fields, coordinator of employer development and student experience. Their energy and authenticity made the session not only impactful but deeply relatable.

The focus of the session was on how we engage when conversations get difficult, how we listen, how we speak, and how we rebuild trust when it breaks. Participants explored how assumptions, tone, and body language can either build or break connection. Using concepts drawn from “Crucial Conversations,” “Radical Candor,” and “How to Hug a Porcupine,” attendees practiced turning emotionally charged conversations into opportunities for clarity, mutual respect, and shared problem-solving.

This session exemplified what EDGE is all about: supporting personal and professional growth through peer-led learning. It was evident that those facilitating weren’t just presenting; they were modeling the very skills they were teaching. The session gave participants space to reflect, connect and engage with strategies they could immediately apply in their own work and relationships.

“We can’t grow or lead without learning how to hear each other especially when it’s hard,” Lang said. “Real communication isn’t just about getting your point across; it’s about creating space for others to be heard.”

Participants left the room with practical tools and stronger connections ready to turn challenging conversations into opportunities for learning, trust, and growth.

Next up: Productivity and AI Tools for Personal Efficiency.

Whiddon COM hosts internal medicine meeting about precision healthcare

Robert Israel, M.D., leads a cooking demonstration for

meeting participants at the teaching kitchen.

Physicians, residents, and medical students recently gathered at the Whiddon College of Medicine for the Alabama Chapter of the American College of Physicians' one-day Winter Scientific Meeting to explore advancements in health and precision medicine.  

The event brought together a diverse group of practitioners and topics, including:  

Errol Crook, Sr., M.D., associate dean for clinical affairs and chief medical officer at Morehouse School of Medicine, who emphasized the importance of using genetics and social factors to provide individualized care that would improve outcomes for patients, especially those from underserved communities.  

Antwan Hogue, M.D., an assistant professor of internal medicine at the Whiddon College of Medicine, senior hospitalist and medical director of the Johnson Haynes, Jr., Comprehensive Sickle Cell Center, who shared insights on using precision medicine to treat sickle cell disease.   

Brian Persing, M.D., a hematologist/oncologist with Singing River Health System, which serves the Mississippi Gulf Coast, discussed the evolving role of personalized treatments in cancer care.  

Robert Israel, M.D., director of USA Health’s Integrative Health and Wellness Program and internal medicine physician, covered how to advise patients on what to eat.  

The meeting ended with an optional hands-on cooking demonstration at the University Commons Teaching Kitchen led by Israel, who emphasizes the power of food as medicine. He regularly shares how plant-forward diets relate to culinary medicine, a relatively new, evidenced-based field that helps people understand how what they eat can help prevent and treat disease.   

Specifically, studies show a plant-forward diet can help decrease the risk of many health conditions and diseases, such as heart disease, stroke, obesity, high blood pressure, high cholesterol, Type 2 diabetes, dementia, and many cancers.   

Founded in 1915, ACP is the largest medical specialty organization in the world with 161,000 members in more than 172 countries. It promotes the science and practice of medicine, and it supports internal medicine physicians in their quest for excellence. ACP and its physician specialist and subspecialists members lead the profession in education, standard-setting, and the sharing of knowledge to advance the science and practice of internal medicine.  

View more photos from the cooking demonstration on Flickr. 

‘IMPROV Your Networking’ event builds student confidence, connection skills

Angie O'Neal, M.Ed., Rachel Cotter, and

Kayla Pavlick, Ph.D.

On March 25, Whiddon College of Medicine students gathered for a unique professional development opportunity titled “IMPROV Your Networking,” an event designed to equip future physicians with essential communication skills for building authentic connections.

Organized by Rachel Cotter, a second-year medical student and the Whiddon College of Medicine delegate to the Medical Association of the State of Alabama (MASA), the event used improvisational activities and reflective discussion to encourage students to approach networking with greater confidence and intentionality.

The session was co-led by Angie O’Neal, M.Ed., director of Learning Support Services, and Kayla Pavlick, Ph.D., assistant professor of medical education. Together, they guided students through interactive exercises focused on “telling your story” by helping students articulate who they are, what motivates them, and how to make memorable first impressions.

“As an introvert, networking can sometimes feel overwhelming or unnatural,” Cotter said. “This event was about helping students feel more comfortable being themselves while making meaningful professional connections.”

The program also served to build enthusiasm for the upcoming MASA Annual Session, scheduled for April 11–13 in Orange Beach. Cotter encouraged her peers to attend the statewide gathering, which brings together physicians, medical students, and healthcare advocates for networking, continuing education, and policy discussions.

“Events like MASA’s Annual Session are where professional relationships begin,” Cotter said. “They’re also where student voices matter. This is how we become part of the larger conversation shaping healthcare in Alabama.”

The Whiddon College of Medicine is proud to support student leaders like Cotter in creating innovative, peer-centered programming that fosters both personal growth and professional development.

For more information about MASA and the Annual Session, visit www.masalink.org.

Medical student awarded scholarship from USA Department of Neurology

From left, Juan Ochoa, M.D., Yulong Huang Stokes, and Bassam Bassam, M.D.

By Milena Mata 

Fourth-year medical student Yulong Huang Stokes recently received the Eran and N.Q. Adams Endowed Scholarship in Autonomic Disorder from the USA Department of Neurology.  

The scholarship was created to support young physicians engaged in neurology who wish to gain a better understanding of dysautonomia. Dysautonomia is an autonomic disorder that affects the involuntary functions of the nervous system such as heart rate. Third- and fourth-year medical students at the Whiddon College of Medicine can apply for this unique research and learning opportunity.  

“On a professional and personal level, Yulong is a very talented and achieved medical student,” said Bassam Bassam, M.D., a professor of neurology at the Whiddon College of Medicine. “She has significant professional and scholastic achievements at an early stage of her medical career. Those achievements, qualifications, and motivation to better understand autonomic disorders clearly qualifies her for receiving the scholarship.” 

Stokes received an undergraduate degree from the University of South Alabama in 2021 and will graduate from the Whiddon College of Medicine in May 2025. With a special interest in epilepsy, Stokes plans to pursue a fellowship after completing her residency in neurology at USA Health. 

“I became interested in neurology after my third-year clerkship,” she said. “I originally thought I should pursue a primary care specialty since I liked everything I did, but I didn’t love anything as much as neurology.” 

Stokes’ skills include differential diagnosis formulation, interdisciplinary collaboration, scientific manuscript writing, patient communication and counseling and navigation of electronic medical records. She has also made writing contributions to five peer-reviewed journal articles.  

After receiving the neurology scholarship, Stokes began research of literature and medical records at USA Health’s Strada Patient Care Center to address the prevalence of symptoms and diagnostic trends in Postural Orthostatic Tachycardia Syndrome (POTS). She detailed changes in the definition of the syndrome, which helped increase awareness. This highlights the importance of specifying the differences between POTS and other medical conditions, Stokes said. 

Juan Ochoa, M.D., a professor of neurology at the Whiddon College of Medicine, said he admires Stokes’ passion for the field.   

“Ms. Stokes’ compassion, resilience, and determination distinguish her as an extraordinary individual who will undoubtedly become an exceptional physician,” Ochoa said. “She has not only shown a profound commitment to her patients but has also demonstrated impressive scholarly aptitude, evidenced by her publication of a peer-reviewed paper during her clerkship rotation. This achievement underscores her intellectual rigor and dedication to advancing the field of neurology.” 

In addition to her academic career, Stokes worked as a clinical skills tutor, a group fitness instructor, and a research lab manager. She has also served as an English tutor, student peer mentor at the USA College of Education and has volunteered at USA Health Children’s & Women’s Hospital.