The Center for Metabolism and Mitochondrial Medicine (C3M), housed within the Department of Medicine, unites scientists, clinicians, and trainees around the shared mission of understanding how mitochondria and metabolism shape health and disease. Founded just over a decade ago to break down silos in cardiovascular and endocrine research, C3M now brings together more than 40 labs across diverse fields, including aging, cancer, pediatrics, psychiatry, pulmonology, immunology, vision, and even space research.
C3M supports research through access to innovative technologies, specialized experimental procedures, and unique reagents that individual labs could not easily access on their own. Since its inception, the center has supported more than 70 investigators across Pitt, assisting with 33 grant submissions over the past year alone. This collaborative model accelerates discovery and ensures that ideas move quickly toward funding, publication, and, ultimately, clinical application.
The center’s reach extends well beyond campus. In partnership with the Center for Immunometabolism (CIM), the Center for Cardiovascular Inflammation (CCVI), and the Division of Endocrinology and Metabolism, C3M launched the Metabolism Consortium, which hosts a weekly seminar series highlighting cutting-edge research in mitochondrial biology and metabolism from Pitt and beyond. Regionally, C3M helps lead the annual Translational Research in Mitochondria, Metabolism, Aging and Disease (TriMAD) meeting, which began as a collaboration among three Pennsylvania institutions and has since expanded across the Midwest. After hosting the meeting in 2023, C3M played a key role in organizing the upcoming 2025 program at the University of Michigan, further cementing Pitt’s role as a regional and national leader in metabolism research.
Why Mitochondria and Metabolism Matter
Mitochondria and metabolism govern how our bodies generate and use energy, and their dysfunction contributes to a wide spectrum of diseases. “These systems drive how our bodies produce and use energy, and their disruptions contribute to a wide range of common diseases,” says Michael Jurczak, PhD, C3M Director of Metabolic Medicine. “Mitochondria not only fuel cells but also regulate processes such as inflammation, cell survival, and stress responses, meaning that when they malfunction, they can accelerate aging and drive conditions like diabetes, neurodegeneration, cancer, and cardiovascular disease.” Even common experiences, like fatigue, muscle weakness, or weight changes, can often be traced back to metabolic dysfunction. For patients living with rare mitochondrial disorders, this research represents an urgent unmet need.
Recent research has revealed surprising connections between metabolism and various physiological processes beyond energy balance. Immune cell function, for instance, is closely linked to metabolic pathways, with changes in glucose or lipid use directly affecting whether immune cells promote inflammation or resolve it. Likewise, metabolism interacts with the brain to regulate appetite and energy use as well as influence mood, cognition, stress, and the risk of neurodegenerative diseases. Even metabolism within the gut microbiome has systemic effects throughout the body by producing metabolites that impact cardiovascular health, immunity, and hormone signaling. These discoveries highlight that metabolism is not just an isolated process, but, rather, it is critical in coordinating communication across organs and systems, making it a key player in both health and disease.
From Mechanisms to Therapeutics
Recent discoveries are redefining the role of mitochondria far beyond energy production. One striking example comes from a C3M collaboration led by Drs. Lan Coffman, Nadine Hempel, Simon Watkins, and Claudette St. Croix, which revealed that ovarian cancer cells can accept mitochondria from surrounding support cells, fueling tumor growth, therapy resistance, and metastasis. This paradigm-shifting discovery not only uncovers a new mechanism of cancer progression but also opens up entirely new avenues for therapy.
In type 2 diabetes, mitochondrial dysfunction contributes to impaired insulin signaling and poor glucose use in tissues like muscle and liver, driving chronically high blood sugar levels. Over time, these metabolic disruptions produce toxic byproducts and oxidative stress, setting the stage for cardiovascular disease, fatty liver disease, and even cancer. Understanding these processes provides an opportunity to identify novel treatment strategies that restore or redirect mitochondrial function to improve long-term outcomes.
Emerging technologies are amplifying these efforts. Advances in single-cell and spatial metabolomics now allow researchers to map mitochondrial activity in unprecedented detail, while new tools like mitochondrial base editors are offering the first glimpses of correcting mutations in mitochondrial DNA. Brett Kaufman, PhD, C3M Director of Bioenergetics and Mitochondrial Medicine, is designing sequence-specific reagents to eliminate harmful mutations in mitochondrial DNA without removing nucleic acids. “There is a huge unmet need in the mitochondrial disease community,” says Kaufman. “These editor-free therapeutics have the potential to make these mutations druggable.”
Other experimental systems like organelle-on-a-chip devices and tissue organoids offer more realistic models for studying how mitochondria respond to stress or therapy. Live-cell biosensors reveal the dynamics of fission, fusion, and mitophagy in real time. On the therapeutic front, targeted drug delivery systems designed to accumulate in mitochondria are opening new options for treating primary mitochondrial diseases, cancer, neurodegeneration, and other metabolic disorders. Together, these innovations aim to deepen our understanding of mitochondrial biology and speed up the development of new treatments.
Bridging Discovery and Clinical Impact
Looking ahead, new technologies are opening exciting opportunities for mitochondrial research. Induced pluripotent stem cells with defined genetic causes of mitochondrial dysfunction are providing powerful models to study metabolism and disease resilience, helping to address the long-standing question of whether mitochondrial dysfunction is a driver or consequence of common diseases. When combined with traditional mouse models, these complementary systems may accelerate the development of therapies that are both mechanistically sound and clinically relevant. Yet significant challenges remain, particularly in the treatment of primary mitochondrial diseases, where no approved therapies currently exist. Moving forward, collaboration among the mitochondrial research community, in collaboration with stakeholders such as the United Mitochondrial Disease Foundation, will be essential to chart new pathways for translating discovery into treatment.
As Pitt’s C3M continues to expand its collaborative networks, train the next generation of scientists, and generate breakthrough discoveries, one message is clear: mitochondria and metabolism are not just topics for the lab. Rather, they are central to understanding, preventing, and treating disease across the lifespan.
To learn more about mitochondrial research in the DOM, visit C3M’s website.