Mitochondria and Their Roles in Health and Disease
Douglas Wallace
Director, Center for Mitochondrial and Epigenomic Medicine (CMEM)
Children's Hospital of Philadelphia
Professor, Department of Pediatrics, Division of Genetic and Genomic Medicine
University of Pennsylvania
Sponsored by PSW Science Members Larry Millstein & Robin Taylor
Video
About the Lecture
Why has Western Medicine failed to understand and prevent the common diseases: neuropsychiatric disorders (depression, autism, schizophrenia), metabolic diseases (diabetes, obesity, cardiovascular disease), neurodegenerative diseases (Alzheimer and Parkinson Disease), cancer, aging?
This lecture will argue that this is due to Kuhnian paradigm crisis. Western Medicine is conceptually based on the anatomical classification of disease (headaches are due to brain problems) and chromosomal genetics (nuclear DNA (nDNA) inherited by the “Laws of Mendel”. Yet to be alive requires energy (vital force), which is systemic and with different organs having different energy requirements (the brain is 2% of body weight but uses 20% of the body’s energy). Moreover, the critical energy genes are located in the maternally inherited mitochondrial DNA (mtDNA) within the cytosolic mitochondria, the power houses of the cell. Therefore, the formula for life becomes: Life = structure (anatomy) + energy (vital force) + information for anatomy and energy.
By not considering mitochondrial energetics and genetics, Western Medicine has overlooked half of the formula for human health, thus failing to understand the causes or to develop cures for common diseases.
To address this glaring deficiency, the lecture will discuss the symbiotic origin of the mitochondrion and its mechanism of energy production; the novel genetics of the mtDNA; using mtDNA variation to reconstruct the origin and ancient migrations of women; demonstrating the mitochondrial etiology of common diseases such as autism, Alzheimer diseases, Type II diabetes and cancer; reporting the importance of mitochondrial dysfunction in Long-COVID; and showing why many common diseases and aging have a delayed onset and progressive course.
Implications/future prospects: If we position energy in the middle of human health rather than anatomy, all of the common diseases, cancer, and aging can be seen as having the same underlying cause, chronic energy deficiency. Mitochondrial bioenergetics and genetics thus promise a whole new approach to sustaining health and treating disease, which includes diet and exercise. In fact, the mitochondrial bioenergetic paradigm of health and disease provides a direct link with traditional healing approaches such as the concept of “Qi” in Traditional Chinese Medicine.
Selected Reading & Media References
Wallace DC. Mitochondrial genetic medicine. Nat Genet. 2018 Dec;50(12):1642-1649. doi: 10.1038/s41588-018-0264-z. Epub 2018 Oct 29. Review. PMID: 30374071
Wallace DC: Mitochondrial DNA Variation in Human Radiation and Disease. Cell 163(1):33-38, Sep 2015 Notes: PMID: 26406369.
Xie W, Murdock DG, Wallace DC. Mitochondria and Qi: Merging eastern and western medicine. Pharmacol Res. 2026 May 12;229:108243. doi: 10.1016/j.phrs.2026.108243. Online ahead of print. PMID: 42119800
About the Speaker
Douglas C Wallace is Professor of Pediatrics in the Division of Human Genetics at the University of Pennsylvania and Director of the Center for Mitochondrial and Epigenomic Medicine at the Children’s Hospital of Philadelphia Research Institute. He also holds the Michael and Charles Barnett Endowed Chair in Pediatric Mitochondrial Medicine and Metabolic Diseases. Previously he was a Professor at the University of California, Irvine where he founded the Center for Molecular and Mitochondrial Medicine and Genetics; and he had faculty appointments at Emory University and at Stanford University.
Doug founded the field of Mitochondrial Medical Genetics. He defined the rules of human mtDNA genetics including demonstrating the maternal inheritance of the human mtDNA. He discovered the first inherited mtDNA diseases; used the accumulation of mtDNA mutations along radiating maternal lineages to reconstruct the origin and ancient migration of women; demonstrated that the accumulation of mtDNA mutations in tissues constitutes an aging clock; linked mitochondrial genetic variation to a wide range of metabolic, degenerative and neuropsychiatric disorders, and showed that mtDNA variation and mitochondrial dysfunction are critical in infectious disease and cancer. He also was the first to discover that mitochondria communicate with each other. Currently he is using mouse models of mitochondrial disease to develop metabolic and genetic therapies for both rare and common diseases with a mitochondrial etiology, and he is investigating potential quantum biology of mitochondrial oxidative phosphorylation.
Doug is an author on more than 500 scholarly publications.
Among other honors and awards, he is a member of the National Academy of Sciences, the National Institute of Medicine and the American Academy of Arts and Sciences. He received the William Allan Award from the American Society of Human Genetics, the Passano Award for mitochondrial genetics, the Gruber Genetics Prize, the American College of Physicians Award for Outstanding Work in Science as Related to Medicine, the Benjamin Franklin Medal for the Life Science, the Janssen Award for Biomedical Research, and Beering Award from Indiana University. He is also the recipient of aa honorary degree in Medicine and Surgery from the University of Padua.
Doug earned a BS in Genetics and Developmental Biology at Cornell University, an MPhil in Microbiology and Human Genetics and a PhD in
Microbiology and Human Genetics at Yale University, and an MD in Mitochondrial Medicine at the University of Padua.