ArticleCritical care (London, England)2026
Plasma mitochondrial-associated proteins scale with illness severity and predict outcome in suspected sepsis.
Article in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMitochondrial dysfunction has been implicated in sepsis-related organ failure. We investigated whether plasma profiles of mitochondrial-associated proteins are associated with illness severity and short-term outcomes and explored whether they reveal distinct mitochondrial subphenotypes.
methodsIn this post hoc analysis of the Acutelines data-biobank, we included 213 adult patients presenting to the emergency department with a suspicion of sepsis, with infection confirmed by independent adjudication. Blood plasma proteins of patients were quantified with the Olink Explore HT platform; of 5,416 proteins, 232 mitochondrial-associated proteins (MitoCarta3.0) were z-standardized and averaged per patient to derive a continuous mitochondrial-protein score. To explore whether operationally distinct patient groups could be identified along this gradient, we additionally performed principal component analysis with K-means clustering on the same protein set. Differential abundance analysis, pathway enrichment, and least absolute shrinkage and selection operator regression were performed as exploratory analyses.
resultsThe continuous mitochondrial-associated protein score increased with illness severity (Spearman ρ 0.18-0.29; p < 0.01) and worse 72-hour outcomes (odds ratio per standard deviation: organ failure-free survival 0.57; intensive care unit admission 1.66; mortality 2.36). Exploratory clustering identified two groups differing mainly in overall mitochondrial-associated protein abundance. Considerable overlap and limited support for a discrete two-cluster structure suggested variation along a continuum rather than clearly distinct mitochondrial subphenotypes. Exploratory pathway analyses implicated mitochondrial metabolism, cellular stress, and injury-related processes.
conclusionsHigher plasma mitochondrial-associated protein abundance was associated with greater illness severity and worse short-term outcomes in suspected sepsis. These associations are hypothesis-generating, providing a first step toward understanding the role of mitochondrial dysfunction in sepsis severity.
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