In seeking to understand mental health and disease, it is fundamental to identify the biological substrates that draw together the experiences and physiological processes that underlie observed psychological changes. Mitochondria are subcellular organelles best known for their central role in energetics, producing adenosine triphosphate to power most cellular processes. Converging lines of evidence indicate that mitochondria play a key role in the biological embedding of adversity. Preclinical research documents the effects of stress exposure on mitochondrial structure and function, and recent human research suggests alterations constituting recalibrations, both adaptive and nonadaptive. Current research suggests dynamic relationships among stress exposure, neuroendocrine signaling, inflammation, and mitochondrial function. These complex relationships are implicated in disease risk, and their elucidation may inform prevention and treatment of stress- and trauma-related disorders. We review and evaluate the evidence for mitochondrial dysfunction as a consequence of stress exposure and as a contributing factor to psychiatric disease.

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