Monday, July 08, 2024

Our well being influences our mitochondrial biology.

I pass on the abstract from Trumoff et al (open source) below. The bottom line is that our experienced well being correlates with with higher levels of energy transformation machinery in our mitochondria.  


Psychosocial experiences predict health trajectories, but the underlying mechanism remains unclear. We report that positive psychosocial experiences are linked to greater abundance of the mitochondrial energy transformation machinery, whereas negative experiences are linked to lower abundance. Overall, psychosocial experiences accounted for 18 to 25% of the variance in protein abundance for complex I, the largest and most upstream mitochondrial oxidative phosphorylation (OxPhos) enzyme. At single-cell resolution, positive psychosocial experiences were particularly related to glial cell mitochondrial phenotypes. As a result, opposite associations between glial cells and neurons were naturally masked in bulk transcriptomic analyses. Our results suggest that mitochondrial recalibrations in specific brain cell types may represent a potential psychobiological pathway linking psychosocial experiences to human brain health.
Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well-being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with single-nucleus RNA sequencing (RNA-seq) revealed strong cell-type-specific associations for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these “mind-mitochondria” associations were masked in bulk RNA-seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self-reported psychosocial experiences are linked to human brain mitochondrial phenotypes.

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