Potential role of mitochondria in stress responses revealed

Written by Alice Weatherston

A recent study exploring the role of mitochondria in the response to mild stress has highlighted potentially broad implications for psychological and neurological conditions. The research carried out in mice indicated that changes in mitochondrial function could lead to psychological alterations in hormonal, metabolic and behavioral systems in response to mild stress. The findings were published recently in the Proceedings of the National Academy of Sciences.
The study was carried out by Douglas Wallace (The Children’s Hospital of Philadelphia), who has over 40 years of experience investigating genetics of mitochondria and their role in health and disease.

During the investigation, Wallace and his team generated standardized mild psychological stress in a cohort of mice by restraining them for a short time period. The effect of the stress on the animals’ neuroendocrine, inflammatory, metabolic and gene transcription systems was then measured. These systems have all been associated with behavioral responses and long-term susceptibility to stress-related diseases in humans.

Relatively minor mutations in mitochondrial genes within the mitochondrial DNA (mtDNA) or nuclear DNA resulted in unique whole-body stress-response signatures highlighted by physiological and gene expression patterns.

Despite it being apparent for some time that individuals respond differently to environmental cues such as stress it has been difficult to identify both the genetics and physiological basis for this. The team therefore believe that their current study provides a potential explanation for this limited understanding, owing to a lack of appreciation for the importance of systematic alterations in energetic metabolism.

“The brain, constituting only 2% of human body weight, consumes 20% of the body’s energy,” commented Wallace. “Hence, mild variations in mitochondrial bioenergetics will have significant effects on the brain.”

“Scientists have long known that stressful experiences, on their own, do not cause disease; it’s our responses to stress that have the potential to culminate in disease. In this emerging paradigm, mitochondria are at the interface of genetic and environmental factors contributing to disease trajectories,” he added.

The study provides a basis for identifying the altered mitochondrial states associated with neuropsychiatric diseases which may ultimately help to highlight new therapies and aid physicians in understanding more fully the effects of environmental stressors on human health.

Wallace concluded: “While human differences in behavior and its relation to predisposition to mental illness as well as to a wide varied of pediatric and adult neurological diseases has been the subject of intense investigations for over a century, we still have a rudimentary understanding of the physiological, genetic, and environmental factors that mediate mental health and illness.  Our recent papers strongly suggest that by reorienting our investigations from the anatomy of the brain and brain-specific genes to the mitochondria and the bioenergetics genes, we may have a more productive conceptual framework to understand neuropsychiatric disease.  If so, this will spawn a whole new generation of neuropsychiatric therapeutics.”

Source: The Children’s Hospital of Philadelphia via PR Newswire