A Platform to Map the Mind-Mitochondria Connection and the Hallmarks of Psychobiology: The MiSBIE Study

Health emerges from coordinated psycho-biological processes powered by mitochondrial energy transformation. But how do mitochondria regulate the multi-system responses that shape resilience and disease risk across the human lifespan? The Mitochondrial Stress, Brain Imaging, and Epigenetics (MiSBIE) study was established to address this question. MiSBIE aims to determine how mitochondria influence the interconnected neuroendocrine, immune, metabolic, cardiovascular, cognitive, and emotional systems. This goal will be achieved by i) studying women and men with genetically defined mitochondrial DNA lesions causing mitochondrial diseases (MitoD) together with individuals spanning the natural spectrum of mitochondrial energy transformation capacity (Control); ii) combining systems-level, physiological, and single-cell methods across biospecimens, along with psychophysiological, self-reported subjective experiences, and neuroimaging modalities; and iii) harnessing complementary baseline, stress-evoked reactivity/recovery, and diurnal assessments including intensive repeated-measures that capture dynamic psychobiological states of allostasis. This interdisciplinary effort is expected to generate new insights into the pathophysiology of mitochondrial diseases, provide a foundation to develop novel biomarkers of human health, and integrate our fragmented knowledge of bioenergetic, brain-body, and mind-mitochondria processes relevant to modern medicine and public health.