Biologist Lynn Margulis postulated in 1967 that mitochondria descend from a bacterium that was engulfed by a larger ancestral cell about 1.5 billion years ago. Instead of consuming this tidbit, the larger cell let it continue living within. Margulis called this event endosymbiosis. (Gray, 2017) which means, roughly, “living or working together from the inside.” The host cell had no energy source that used oxygen—which, thanks to plants, was already abundant in the atmosphere; mitochondria filled this gap. The unlikely union allowed cells to communicate and cooperate and let their awareness (McMillen & Levin, 2024) expand beyond their own boundaries, enabling a more complex future in the form of multicellular animals. Mitochondria made cells social, binding them in a contract whereby the survival of each cell depends on every other one, and thus made us possible.
Mitochondria are themselves social beings. (Picard & Sandi, 2021) At least, they foreshadow sociality. Like the bacterium they descended from, they have a life cycle: old ones die out, and new ones are born out of existing ones. Communities of these organelles live within each cell, usually clustered around the nucleus. Mitochondria communicate, both within their own cells and among other cells, reaching out to support one another in times of need and generally helping the community flourish. They produce the heat that keeps our bodies warm. They receive signals about aspects of the environment in which we live, such as air pollution levels and stress triggers, and then integrate this information and emit signals such as molecules that regulate processes within the cell and, indeed, throughout the body.
We inherit our mitochondria from our mother—from the egg cell, to be precise. Mitochondria have their own DNA, which consists of only 37 genes, compared with the thousands of genes in the spiraling chromosomes inside the cell nucleus. This ring of mitochondrial DNA, or mtDNA, is sheltered within two membranes. The outer shell, shaped like the skin of a sausage, encases the mitochondrion and selectively allows molecules to enter or exit. The outer shell, shaped like the skin of a sausage, encases the mitochondrion and selectively allows molecules to enter or exit. The inner membrane is made of densely packed proteins and has many folds, called cristae, which serve as a site for chemical reactions, much like the plates suspended inside a battery.
In the 1960s British biochemists Peter Mitchell and Jennifer Moyle discovered how electrons derived from carbon in food combine with oxygen in the cristae, releasing a spark of energy that is captured as a gradient (Mitchell, 1961) in electrical voltage across the membrane. This voltage provides the driving force for all processes in the body and brain, from warming to manufacturing molecules to thinking. Mitochondria also produce a molecule called adenosine triphosphate, which serves as a portable unit of energy that powers hundreds of biochemical reactions within each cell.
Since the emergence of molecular biology and the discovery of pathogenic mitochondrial DNA defects in the 1980’s, research advances have revealed a number of common human diseases which share an underlying pathogenesis involving mitochondrial dysfunction. Mitochondria undergo function-defining dynamic shape changes, communicate with each other, regulate gene expression within the nucleus, modulate synaptic transmission within the brain, release molecules that contribute to oncogenic transformation and trigger inflammatory responses systemically, and influence the regulation of complex physiological systems. Novel mitopathogenic mechanisms are thus being uncovered across a number of medical disciplines including genetics, oncology, neurology, immunology, and critical care medicine. Increasing knowledge of the bioenergetic aspects of human disease has provided new opportunities for diagnosis, therapy, prevention, and in connecting various domains of medicine. In this article, we overview specific aspects of mitochondrial biology that have contributed to - and likely will continue to enhance the progress of modern medicine. (Picard et al., 2016) (Picard, 2025)